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Background: We studied the effects of 5 vasopressors on fetal arterial perfusion pressure (FAP) in vitro using the dual perfused, single isolated cotyledon, human placental model., Methods: In 29 separate experiments, epinephrine (75 mg), norepinephrine (75 mg), ephedrine (50 mg), phenylephrine (2 mg), and methoxamine (40 mg) were introduced into the 250-mL reservoir serving the maternal perfusion circuit to determine the effect of each drug on FAP. The duration of drug exposure for each placental cotyledon was approximately 180 minutes., Results: After 180 minutes, FAP (mean +/- sd) increased significantly with ephedrine from 64 +/- 3 to 172 +/- 71 mm Hg (P < 0.001) and with phenylephrine from 81 +/- 4 to 132 +/- 11 mm Hg (P = 0.003). No changes in FAP were seen with epinephrine, norepinephrine, and methoxamine., Conclusions: In the dual perfused, single isolated cotyledon, human placental model, exposure of the maternal circulation to ephedrine and phenylephrine caused an increase in FAP, whereas exposure to norepinephrine, epinephrine, and methoxamine did not. The pharmacodynamic mechanisms underlying these differences have yet to be explained. Thus, the clinical implications of the findings are as yet unclear.

This article examines the transitions in pharmacological therapy for obesity. It reviews the current options approved by the Food and Drug Administration and several drugs approved for other indications that can be used to treat obesity as well. Because weight regulation is complex and redundant systems protect against perceived starvation, optimal treatment of obesity in individual patients will likely require different combinations of behavioral, nutritional, pharmacologic, endoscopic, and surgical therapies., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Ephedrine (Eph) is an alkaloid extracted from the Chinese traditional medicine plant Ephedra Sinica or Ma huang, which has been known for effects on the central nervous system, cardiovascular system, and smooth muscles. However, the corresponding molecular mechanism of these effects remains unknown. In this study, we investigated the influences of Eph on heart rate, QTc interval in vivo, and the slowly activated K channels (IKs) that were composed of both KCNQ1 and KCNE1 subunits in vitro. Results demonstrated that Eph, but not pseudoephedrine, could increase the heart rate and shorten QTc interval of BALB/c mouse. Besides, Eph markedly activated cardiac IKs currents with EC50 = 50 nM and shifted G-V curves to left. But pseudoephedrine had no effects on Iks currents. The onset and offset time constants of IKs currents activated by Eph at 1 M were tauon = 49 seconds and tauoff = 400 seconds. A pair of binding sites of Eph on KCNQ1/KCNE1 channel was also shown to occur at F296 and Y299 in the S5-S6 P-loop of the KCNQ1 channel. As both amino acids are highly conserved in the KCNQ family, Eph can possibly activate other members of the KCNQ family. The mechanism of Iks activated by Eph may provide a clue for drug design in the future.

Objective: To discuss the significance of processing and complex prescription with Herba Ephedrae, the effects of Herba Ephedrae, Honey-fried Herba Ephedrae and Maxingshigan decoction on autonomic activities in mice were compared., Methods: 110 female Kunming mice were divided into 11 groups, namely normal saline group (NS), ephedrine group (E), high dose Herba Ephedrae group (MH-H), moderate dose Herba Ephedrae group (MH-M), low dose Herba Ephedrae group (MH-L) ,high dose Honey-fried Herba Ephedrae group (ZMH-H), moderate dose Honey-fried Herba Ephedrae group (ZMH-M),low dose Honey-fried Herba Ephedrae group (ZMH-L), high dose Maxingshigan decoction group (MX-H), moderate dose Maxingshigan decoction group (MX-M) and low dose Maxingshigan decoction group (MX-L). The numbers of autonomic activity in 15 minutes before intragastric administration (ig), and after ig 0.5, 1, 2, 3, 4 h were determined., Results: There was interaction between time and groups. There were very significant differences between before ig and all time-points after ig (P < 0.01). 30 minutes after ig,there were significant differences between E and NS,E and ZMH-L,E and MX-L (P < 0.05). 1 h after ig, there were significant differences between MX-M and NS (P < 0.05). 3 h after ig, there were significant differences between MX-M and MH-L (P < 0.05). 30 minutes after ig, both ZMH-L and MX-L could reduce the number of autonomic activity in some extent compare with MH-L. 1 h or 2 h after ig, ZMH-L could reduce the number of autonomic activity in some extent compare with MH-L 4 h after ig, MX-L could reduce the number of autonomic activity in some extent compare with MH-L., Conclusion: Under the condition of this study, regarding autonomic activity as index, both ZMH-L and MX-L can reduce center stimulation in some extent.

Perinatal hypoxic-ischemic (HI) is a major cause of brain injury in the newborn, and there is a lack of effective therapies to reduce injury-related disorders. The aim of the present study was to evaluate the effect of a combination of ephedrine and hyperbaric oxygen (HBO) on neonatal hypoxic-ischemic brain injury. 7-day-old Sprague-Dawley rat pups were randomly divided into sham operation, HI, ephedrine, HBO, and combined group. The ephedrine group was intraperitoneally injected with ephedrine, HBO group was treated for 2h at 2.5 absolute atmosphere (ATA) per day, the combined group received both ephedrine and HBO treatments, the sham operation and HI groups were intraperitoneally injected with normal saline. Rat brains at 7 days after HI, were collected to determine histopathological damage and the expression levels of Caspase-3 and Nogo-A. Four weeks after insult, animals were challenged with Morris water maze test. The expressions of Caspase-3 and Nogo-A were reduced in treating groups compared to those in HI group (P<0.01). Compared with the single treatment groups, the expression levels of Caspase-3 and Nogo-A were significantly reduced in the combined group (P<0.01). Compared with the single treatment groups, the average time of escape latency was significantly shorter (P<0.01) and the number of platform location crossing was more (P<0.05) in combined group. These findings indicate that the combination of ephedrine and HBO can enhance the neuroprotective effect in the neonatal rat HI model partially mediated by inhibiting Caspase-3 and Nogo-A pathways.

Background: Hemodynamic responses to vasopressors used during spinal anesthesia for elective Cesarean delivery, have not been well described. This study compared the effects of bolus phenylephrine and ephedrine on maternal cardiac output (CO). The hypothesis was that phenylephrine, but not ephedrine, decreases CO when administered in response to hypotension during spinal anesthesia., Methods: Forty-three patients were randomized to receive 80 microg of phenylephrine or 10 mg of ephedrine. Both pulse wave form analysis and transthoracic bioimpedance changes were used to estimate stroke volume in each patient. Hemodynamic responses to spinal anesthesia and oxytocin were also recorded. A subgroup of 20 patients was randomized to receive oxytocin compared with oxytocin plus 80 microg of phenylephrine after delivery., Results: Mean CO and maximum absolute response in CO were significantly lower during the 150 s after phenylephrine administration than after ephedrine (6.2 vs. 8.1 l/min, P = 0.001, and 5.2 vs. 9.0 l/min, P < 0.0001, respectively for pulse wave form analysis, and 5.2 vs. 6.3 l/min, P = 0.01 and 4.5 vs. 6.7 l/min, P = 0.0001, respectively for bioimpedance changes). CO changes correlated with heart rate changes. Coadministration of phenylephrine obtunded oxytocin-induced decreases in systemic vascular resistance and increases in heart rate and CO. Trends in CO change were similar using either monitor., Conclusions: Bolus phenylephrine reduced maternal CO, and decreased CO when compared with ephedrine during elective spinal anesthesia for Cesarean delivery. CO changes correlated with heart rate changes after vasopressor administration, emphasizing the importance of heart rate as a surrogate indicator of CO. Coadministered phenylephrine obtunded hemodynamic responses to oxytocin.

Background: Prophylactic infusion of phenylephrine to prevent hypotension at Caesarean section has been shown to decrease the rostral spread of intrathecal plain levobupivacaine and intrathecal hyperbaric bupivacaine by a median of two dermatomes compared with ephedrine. The aim of this study was to determine the median effective dose (ED50) of intrathecal bupivacaine required to achieve a block to touch at the xiphisternum in patients undergoing Caesarean section when phenylephrine or ephedrine are used to prevent hypotension., Methods: Seventy women were randomized in two groups to receive either phenylephrine at a rate of 16.6 microg min(-1) (concentration 1microg ml(-1)) or ephedrine at a rate of 1.5 mg min(-1) (concentration 90 microg ml(-1)). Patients received varying doses of hyperbaric bupivacaine with fentanyl 25 microg using a double-blinded, up-down sequential allocation design. Effective doses were defined as anaesthesia to touch with ethyl chloride spray to the xiphisternum within 20 min., Results: The ED50 estimates of bupivacaine were similar in the two groups: 7.8 mg [95% confidence interval (CI) 6.7-8.9] with phenylephrine and 7.6 mg (95% CI 6.8-8.4) with ephedrine. Systolic blood pressure control was similar (P=0.18) with vasopressors but heart rate was higher with ephedrine (P=0.0014)., Conclusions: Under the conditions of this study, we have shown that when phenylephrine or ephedrine were used to prevent post-spinal hypotension, the dosing requirement of hyperbaric bupivacaine was similar for intrathecal anaesthesia.

To determine if the preanesthetic administration of ephedrine would prevent anesthesia-induced hypotension in dogs and cats, 10 cats were anesthetized with acepromazine, butorphanol, ketamine, and isoflurane, and 8 dogs were anesthetized with acepromazine, morphine, propofol, and halothane. Cats received ephedrine or saline 10 minutes after premedication. Dogs received ephedrine or saline at the time of premedication. Systolic arterial blood pressure, respiratory rate, heart rate, end-tidal CO2, O2 saturation, cardiac rhythm, and rectal temperature were recorded.The systolic arterial pressure in cats receiving saline was significantly lower than baseline at 10 minutes after premedication, and systolic arterial pressure was < 80 mmHg for the duration of anesthesia. In cats receiving ephedrine, the systolic arterial pressure was significantly lower than baseline for the duration of anesthesia, but systolic arterial pressure was not < 80 mmHg until 25 min after induction. In dogs, systolic arterial pressure was significantly lower than baseline by 5 and 40 min after pre-medication in dogs receiving saline and ephedrine, respectively. There was no difference in heart rate, respiratory rate, end-tidal CO2, rectal temperature, O2 saturation, or cardiac rhythm among treatment groups. Prophylactic ephedrine delayed, but did not prevent, the onset of hypotension.

Norepinephrine and dopamine are both believed to affect signal-to-noise in the cerebral cortex. Dopaminergic agents appear to modulate semantic networks during indirect semantic priming, but do not appear to affect problem solving dependent on access to semantic networks. Noradrenergic agents, though, do affect semantic network dependent problem solving. We wished to examine whether noradrenergic agents affect indirect semantic priming. Subjects attended three sessions: one each after propranolol (40 mg) (noradrenergic antagonist), ephedrine (25 mg) (noradrenergic agonist), and placebo. During each session, closely related, distantly related, and unrelated pairs were presented. Reaction times for a lexical decision task on the target words (second word in the pair) were recorded. No decrease in indirect semantic priming occurred with ephedrine. Furthermore, across all three drugs, a main effect of semantic relatedness was found, but no main effect of drug, and no drug/semantic relatedness interaction effect. These findings suggest that noradrenergic agents, with these drugs and at these doses, do not affect indirect semantic priming with the potency of dopaminergic drugs at the doses previously studied. In the context of this previous work, this suggests that more automatic processes such as priming and more controlled searches of the lexical and semantic networks such as problem solving may be mediated, at least in part, by distinct mechanisms with differing effects of pharmacological modulation.

Background and Objectives: Combined spinal and epidural anaesthesia (CSEA) has previously been shown to result in a higher sensory block than equivalent single shot spinal anaesthesia (SSSA). In nonpregnant patients, hypotension was also more pronounced in the CSEA group. The aim of this randomized trial was to compare the haemodynamic stabilities of CSEA and SSSA during elective caesarean section when the same dose of anaesthetic was administered. This was studied directly by measuring the noninvasive arterial blood pressure (BP) and indirectly by the amount of ephedrine required to maintain baseline BP. Systemic vascular resistance index (SVRI) and cardiac index (CI) were also measured using thoracic impedance cardiography., Methods: Seventy women received hyperbaric bupivacaine (12.5 mg) and diamorphine (0.3 mg) intrathecally via either CSEA or SSSA. Noninvasive arterial BP, CI and SVRI were measured every 2 min. The total ephedrine used was calculated., Results: There were no significant differences between the groups in ephedrine requirements (P = 0.38), intraoperative mean arterial pressure (P = 0.77), CI (P = 0.17) or SVRI (P = 0.10)., Conclusion: CSEA placement appears to offer no haemodynamic benefits compared with SSSA when the same dose of local anaesthetic is administered.

Background and Objectives: Hypotension during spinal block for cesarean section is secondary to the sympathetic blockade and aorto-caval compression by the uterus and it can be deleterious to both the fetus and the mother. Ephedrine and phenylephrine improve venous return after sympathetic blockade during the spinal block. The objective of this study was to compare the efficacy of ephedrine and phenylephrine in the prevention and treatment of maternal hypotension during spinal block and to evaluate their side effects and fetal changes., Methods: Sixty patients undergoing spinal block with bupivacaine and sufentanil for cesarean section were randomly divided in two groups to receive prophylactic ephedrine (Group E, n = 30, dose = 10 mg) or phenylephrine (Group P, n = 30, dose = 80 microg). Hypotension (blood pressure equal or lower than 80% of baseline values) was treated with bolus administration of the vasoconstrictor at 50% of the initial dose. The incidence of hypotension, reactive hypertension, bradycardia, and vomiting, and Apgar scores on the 1st and 5th minutes, and blood gases of the umbilical cord blood were evaluated., Results: The mean dose of ephedrine used was 14.8 +/- 3.8 mg and of phenylephrine was 186.7 +/- 52.9 microg. Demographic parameters and the incidence of vomiting, bradycardia, and reactive hypertension were similar in both groups. Hypotension had an incidence of 70% in Group E and 93% in Group P (p < 0.05). The mean arterial pH of the umbilical cord blood and the Apgar score in the 1st minute were lower in Group E (p < 0.05). Differences in the Apgar score in the 5th minute were not observed., Conclusions: Ephedrine was more effective than phenylephrine in the prevention of hypotension. Both drugs had similar incidence of side effects. Fetal repercussions were less frequent with phenylephrine and were transitory with the use of ephedrine.

Selective serotonin reuptake inhibitors (SSRIs) are associated with significant sexual side effects. By definition, all SSRIs increase overall serotonin (5HT) by binding to serotonin autoreceptors (5HT(IA)); however, each SSRI has a unique portfolio of secondary binding properties to other neurotransmitters such as norepinephrine (NE). As 5HT(IA) receptors mediate NE neurotransmission, SSRIs that are highly selective for 5HT(IA) are more likely to reduce NE efficiency; however, in SSRIs that are less selective for 5HT(IA), this could be counteracted by secondary binding to NE. Norepinephrine is the major neurotransmitter of the sympathetic nervous system (SNS), which has been shown to mediate genital arousal in women; thus, it is possible that increasing SNS activity in women taking SSRIs that are highly selective for 5HT(IA) may counteract sexual side effects in those women. To test this hypothesis, we conducted a reanalysis of Meston (2004)'s 8-week, double-blind, cross-over, placebo-controlled study of the effects of ephedrine (50 mg taken 1 h prior to sexual activity) on self-reported sexual functioning of women taking paroxetine (N = 5), sertraline (N = 7), or fluoxetine (N = 7). As predicted, women taking SSRIs, which are highly selective for 5HT(IA) (sertraline, paroxetine), showed improvement in sexual arousal and orgasm. By contrast, women taking SSRIs, which are less selective for 5HT(IA) relative to NE (fluoxetine), showed no change or decrease in sexual functioning. These findings have implications for treating certain SSRI-induced sexual side effects.

Oseltamivir (Tamiflu), a neuraminidase inhibitor, is widely used for treatment of influenza. Because abnormal behaviors have been observed in some Japanese teenagers following oseltamivir use, its safety has been questioned. Oseltamivir is known to alter neuronal function and behavior in animals, particularly when administered in combination with ethanol. Based on this, it has been hypothesized that interactions of oseltamivir with other drugs may result in altered CNS excitability in this study. It has been found that injection of ephedrine and caffeine overcame inactivity induced by oseltamivir and ethanol but did not alter changes in novelty seeking behavior in a Y-maze test. In ex-vivo hippocampal slices, oseltamivir carboxylate (OTC), an active form of oseltamivir, alters excitability in the absence of ethanol. In slices pretreated with OTC, long-term depression (LTD), a form of synaptic plasticity that is correlated with Y-maze performance was not altered if caffeine or ephedrine was administered individually. However, LTD could not be induced in slices pretreated with OTC if caffeine and ephedrine were administered simultaneously. These observations suggest that combination of oseltamivir with other neurostimulants may alter synaptic plasticity and this may contribute to behavioral changes associated with the drug.

Background: Phenylephrine and ephedrine are both used to maintain arterial blood pressure during spinal anesthesia for cesarean delivery. Usually, either drug is given alone but several previous studies have described combining the drugs. However, the effect of varying the proportion of vasopressors in such combinations has not been reported., Methods: One-hundred-twenty-five parturients having spinal anesthesia for elective cesarean delivery were randomized to receive an IV infusion of phenylephrine and ephedrine combined in one of five different concentration ratios. Assuming phenylephrine 100 microg to be approximately equipotent to ephedrine 8 mg, the groups contained the proportional potency equivalent of 100%, 75%, 50%, 25% or 0% of phenylephrine and 0%, 25%, 50%, 75% or 100%, respectively, of ephedrine. The infusions were adjusted to maintain systolic blood pressure (SBP) near baseline until uterine incision. Hemodynamic changes and umbilical cord blood gases were compared., Results: As the proportion of phenylephrine decreased and proportion of ephedrine increased among the groups, the following significant trends were detected: the incidences of hypotension and nausea/vomiting increased, the median magnitude of deviations of SBP above or below baseline and the bias for SBP to be above baseline increased, maternal heart rate was faster, fetal pH and base excess decreased, umbilical arterial oxygen content decreased and umbilical venous Po2 increased., Conclusions: When varying combinations of phenylephrine and ephedrine were given by infusion to maintain arterial blood pressure during spinal anesthesia for cesarean delivery, as the proportion of phenylephrine decreased and the proportion of ephedrine increased, hemodynamic control was reduced and fetal acid-base status was less favorable. Combinations of phenylephrine and ephedrine appear to have no advantage compared with phenylephrine alone when administered by infusion for the prevention of hypotension associated with spinal anesthesia for cesarean delivery.

We postulated that the onset time of rocuronium can be accelerated effectively if it is administered at the time when the effect of ephedrine on cardiac output has reached its maximum. Seventy-five male, anaesthetised, patients were randomly allocated to three groups. Ephedrine 70 microg.kg(-1) was administered at 4 min (Early) or 30 s (Late) before administering rocuronium. The control group received saline at 4 min and at 30 s before rocuronium. The onset time of rocuronium in the Early group was significantly shorter than in the Control group, but there was no difference in the onset time between the Late and Control groups. There were no significant differences in the intubating conditions of the three groups. Ephedrine 70 microg.kg(-1) can reduce the onset time of rocuronium effectively if rocuronium is administered at 4 min following the ephedrine injection, when the effect of ephedrine on cardiac output is expected to reach its maximum.

To compare the mechanisms underlying mechanical responses to ephedrine and Ephedra herb, a main component of Kakkon-to, in isolated male and female rabbit urinary bladder and urethral strips, responses of isolated strips to the agents were recorded in organ bath systems. Ephedrine and Ephedra herb relaxed the female urinary bladder to the similar extent. These relaxations are reversed to contractions by timolol. In the presence of timolol, ephedrine produced less contraction of urethral strips in the female than those in the male; this contraction was abolished by prazosin. Ephedra herb contracted the female urethra less than that of the male, and the contraction was stronger than that by ephedrine. The contraction caused by Ephedra herb in strips treated with timolol was significantly inhibited by prazosin. The prazosin-resistant contraction of the female urethra was greater than that of the male. Quinacrine, a phospholipase A(2) inhibitor, indomethacin, and AA861, a 5-lipoxygenase inhibitor, inhibited the contraction. The contraction was inhibited by ZK 158252, a leukotriene (LT) B(4)-receptor antagonist. These findings suggest that Ephedra herb contracts the urethra via arachidonic acid metabolites together with alpha(1)-adrenoceptor stimulation. The metabolites produced by 5-lipoxygenase may stimulate LTB(4), but not CysLt(1), receptors. These contractile components induced by Ephedra herb and Kakkon-to might be effective for the treatment of stress urinary incontinence.

Cardiac surgery causes an acute inflammatory response and organ damage. In this study, for the first time in the literature, we compared the effects of priming solutions at 20 degrees C and 36 degrees C on acute inflammatory markers and hemodynamic parameters. Forty patients were recruited and randomized into two groups, each consisting of 20 participants who underwent elective coronary artery bypass grafting operation. Groups were primed with the same solution at different temperatures. Hemodynamic parameters were recorded. Blood samples were drawn pre-operatively and at the 15(th) and 60(th) minutes of aortic cross-clamping and the 24(th) hour following surgery. Serum pre-albumin, alpha-1 antitrypsin, and tumor necrosis factor-alpha levels were determined. The groups were compared statistically. Both of the groups were comparable for mean aortic cross-clamping time and mean time for cardiopulmonary bypass. Mean blood pressure value was significantly lower and the mean amount of ephedrine hydrochloride used was significantly higher in the cold priming group. Spontaneous beating of the heart after removal of aortic cross-clamp significantly was more frequent in the warm priming group. A significant rise was observed in systemic inflammatory markers in the cold priming group. In our study, the lesser amount of ephedrine hydrochloride used and the higher frequency of spontaneous beating of the heart in the warm priming group may be considered as improvements in hemodynamic status. Use of warm priming solution also induced a significant improvement in the acute inflammatory markers. We recommend the use of warm priming solution in open heart surgery.

The purpose of this study was to investigate the effects of ephedrine, an alpha,beta-adrenoceptor agonist, on the regulation of human nasal ciliary beat frequency (CBF). Changes in (cultured) human nasal CBF in response to 0.25, 0.5, 1.0 and 2.0% ephedrine were quantified by using high-speed (240 frames per second) digital microscopy combined with a beat-by-beat CBF analysis. At approximately 25 degrees C, we found that ephedrine induces an instant and moderate increase in human nasal CBF followed by an inhibitory response. With concentrations ranging from 0.25 to 2.0%, while the increment is independent of ephedrine concentration, the inhibitory effect is dependent on the concentration of ephedrine. Based on these results we propose that the clinically used concentration of ephedrine, 0.5%, has maximum stimulatory effect without obvious inhibitory effect on (cultured) human nasal CBF.

Changes in the sensitivity of response distributions to changes in reward distribution (reinforcer distribution sensitivity) were examined when rats were exposed to low and moderate doses of caffeine, ephedrine, and caffeine-ephedrine combinations. The data show significant decreases in sensitivity in response distributions to changes in reward schedule values during exposure to caffeine and ephedrine/caffeine combinations, whereas ephedrine alone resulted in overmatching comparable with baseline and NaCl conditions. Rats treated either with 3.0-mg/kg or 10.0-mg/kg doses of caffeine and all combinations of ephedrine at doses of 1.8 or 5.6 mg/kg with caffeine at 3.0 or 10.0 mg/kg showed reduced sensitivity in response distributions to differences in reinforcement schedule ratios. In contrast, when rats were exposed to ephedrine at 1.8 or 5.6 mg/kg, they maintained or increased the degree of overmatching. Although reinforcer distribution sensitivity was altered, drug exposure did not significantly affect the absolute rates of responding. Bias varied after exposure to caffeine, ephedrine, and their combinations, but not systematically. Finally, whereas the estimates of goodness of fit (r2) to the matching equation showed some decreases during drug exposure, these were neither statistically significant nor correlated with drug dose. These results suggest differential effects of ephedrine and caffeine on the sensitivity of response distributions to changes in reinforcement ratio distributions, with deleterious effects of caffeine and ephedrine/caffeine combinations.

Objective: To determine the cardiovascular responses of ephedrine and dopamine for the management of presurgical hypotension in anesthetized dogs., Study Design: Prospective, randomized, clinical trial., Animals: Twelve healthy client-owned dogs admitted for orthopedic surgery; six per group, Methods: Prior to surgery, 58 anesthetized dogs were monitored for hypotension [mean arterial pressure (MAP) <60 mmHg] that was not associated with bradycardia or excessive anesthetic depth. Ephedrine (0.2 mg kg(-1), IV) or dopamine (5 microg kg(-1) minute(-1), IV) was randomly assigned for treatment in 12 hypotensive dogs. Ten minutes after the first treatment (Tx(1)-10), ephedrine was repeated or the dopamine infusion rate was doubled. Cardiovascular assessments taken at baseline, Tx(1)-10, and 10 minutes following treatment adjustment (Tx(2)-10) were compared for differences within and between treatments (p < 0.05)., Results: Ephedrine increased cardiac index (CI), stroke volume index (SVI), oxygen delivery index (DO(2)I), and decreased total peripheral resistance (TPR) by Tx(1)-10, while MAP increased transiently (<5 minutes). The second ephedrine bolus produced no further improvement. Dopamine failed to produce significant changes at 5 microg kg(-1) minute(-1), while 10 microg kg(-1) minute(-1) increased MAP, CI, SVI significantly from baseline, and DO(2)I compared with Tx(1)-10. The improvement in CI, SVI, and DO(2)I was not significantly different between treatments at Tx(2)-10., Conclusions and Clinical Relevance: In anesthetized hypotensive dogs, ephedrine and dopamine improved cardiac output and oxygen delivery. However, the pressure-elevating effect of ephedrine is transient, while an infusion of dopamine at 10 microg kg(-1) minute(-1) improved MAP significantly by additionally maintaining TPR.

Background: We hypothesized that the administration of ephedrine and phenylephrine for maternal hypotension modifies cardiovascular hemodynamics in near-term sheep fetuses., Methods: At 115-136 days of gestation, chronically instrumented, anesthetized ewes with either normal placental function or increased placental vascular resistance after placental embolization were randomized to receive boluses of ephedrine (n = 12) or phenylephrine (n = 12) for epidural-induced hypotension after a short period of hypoxemia. Fetal cardiovascular hemodynamics were assessed by Doppler ultrasonography at baseline, during hypotension and after vasopressor treatment., Results: During hypotension, fetal PO(2) decreased and proximal branch pulmonary arterial and pulmonary venous vascular impedances increased. Additionally, in the embolized fetuses, the time-velocity integral ratio between the antegrade and retrograde blood flow components of the aortic isthmus decreased. These parameters were restored to baseline conditions by ephedrine but not by phenylephrine. With phenylephrine, weight-indexed left ventricular cardiac output and ejection force decreased in the non-embolized fetuses, and the proportion of isovolumetric contraction time of the total cardiac cycle was elevated in the embolized fetuses., Conclusions: After exposure to hypoxemia and maternal hypotension, ephedrine restored all fetal cardiovascular hemodynamic parameters to baseline. Phenylephrine did not reverse fetal pulmonary vasoconstriction or the relative decrease in the net forward flow through the aortic isthmus observed in fetuses with increased placental vascular resistance. Moreover, fetal left ventricular function was impaired during phenylephrine administration.

Objective: To study the effect of ephedrine on neural plasticity after hypoxic-ischemic brain damage (HIBD) in neonatal rats., Method: Sixty SD rats, aged 7 days, were made as HIBD model, which were randomly divided into following 4 groups, an ephedrine group, a D-amphetamine (D-AMPH) group, a cytodine triphosphate-2Na (CTP) group and a ganglioside (GMI) group. Changes in the expression of growth-associated protein-43 (GAP-43) and synaptophysin (SYP) in the hippocampal area CA3 were detected with immunohistochemical method. Four weeks after the operation, learning and memory test in Morris water maze was performed for 5 days., Result: (1) The GAP-43 and SYP expression levels in hippocampal area CA3 in the ephedrine group were higher than those in the spontaneous recovery group (P < 0.05), with no significantly different from those the CTP group and the D-AMPH group. (2) The average escape latency in the ephedrine group, the D-AMPH group and the CTP group were significantly shorter than that in the spontaneous recovery group (P < 0.05), and the frequency passing the original platform in the 3 treatment groups were significantly more than those in the spontaneous recovery group (P < 0.01). The escape latency was longer and the frequency passing the original platform was less in the ephedrine group than that in the GM1 group, with no significant differences as compared with the CTP group and the D-AMPH group., Conclusion: Ephedrine can enhance spatial orientation and learning and memory abilities of HIBD rats in later life. This protective effect is associated with decrease of neuronal loss after HIBD, and promotion of the expression of GAP43 and SYP. Ephedrine can exert the same protection against HIBD as D-AMPH and CTP do, but the amelioration of spatial orientation and learning and memory abilities by ephedrine in later life in rats after HIBD is slightly weaker than that by GM1, which is possibly related with the dose of ephedrine.

Background: Maternal hypotension occurs in 60-94% of Cesarean deliveries with 10-15 mg spinal bupivacaine. Reduced doses of bupivacaine may decrease the incidence of hypotension, nausea, and vasopressor use. The primary objective of this study was to compare 4.5 mg and 12 mg doses of intrathecal bupivacaine on maternal hemodynamics. The secondary objective was to determine if anticipated reductions in side effects were reflected in increased patient satisfaction., Methods: Following Research Ethics Board approval and informed consent 52 term parturients undergoing elective Cesarean delivery were randomly assigned to isobaric bupivacaine 4.5 mg or hyperbaric bupivacaine 12 mg for spinal anesthesia. All patients received fentanyl 50 microg and morphine 200 microg intrathecally. Intravenous fluid and vasopressor administration were standardized. Maternal hemodynamics, and sensorimotor levels were recorded at regular intervals. Side effects and patient satisfaction were documented., Results: Median cepahalad sensory block was C8 in both groups (NS) but the intensity of motor block was significantly less (P < 0.001) and of shorter duration (P < 0.001) with bupivacaine 4.5 mg. The proportion of patients requiring ephedrine (> 70%) and the quantities of ephedrine used were similar in both groups (NS). Use of supplemental analgesia, side effects, and measures of patient satisfaction were comparable in both groups., Discussion: Intrathecal bupivacaine 4.5 and 12 mg yielded similar sensory block and side effects during Cesarean delivery. Patients receiving 4.5 mg did, however, experience significantly less motor blockade of shorter duration.

Ephedra species of plants have both beneficial and adverse effects primarily associated with the presence of ephedrine alkaloids. Few reports have appeared that examine the direct actions of ephedrine alkaloids on human subtypes of adrenergic receptors (ARs). In the present study, ephedrine alkaloids were evaluated for their binding affinities on human alpha(1A)-, alpha(1B)-, alpha(1D)-, alpha(2A)-, alpha(2B)-, and alpha(2C)-AR subtypes expressed in HEK and Chinese hamster ovary cells. Cell-based reporter gene assays were used to establish functional activity of ephedrine alkaloids at alpha(1A)-, alpha(2A)-, and alpha(2C)-ARs. The data showed that ephedrine alkaloids did not activate alpha(1)- and alpha(2)-ARs and that they antagonized the agonist-mediated effects of phenylephrine and medetomidine on alpha(1)- and alpha(2)-ARs, respectively. As in the binding studies, 1R,2R- and 1R,2S-ephedrine showed greater functional antagonist activity than the 1S,2R- and 1S,2S-isomers. The rank order of affinity for the isomers was 1R,2R > 1R,2S > 1S,2R > 1S,2S. The rank order of potencies of alkaloids containing a 1R,2S-configuration was norephedrine > or = ephedrine >> N-methylephedrine. These studies have demonstrated that orientation of the beta-hydroxyl group on the ethylamino side chain and the state of N-methyl substitution are important for alpha-AR binding and functional activity of the ephedrine alkaloids. In conclusion, the ephedrine isomers and analogs studied did not exhibit any direct agonist activity and were found to possess moderate antagonist activities on cloned human alpha-ARs. The blockade of presynaptic alpha(2A)- and alpha(2C)-ARs may have a pharmacological role in the direct actions of Ephedra alkaloids.

Unlabelled: This study evaluated the effect of various beta-adrenergic agonists on (18)F-FDG uptake in brown adipose tissue (BAT) in rats using ex vivo biodistribution studies., Methods: Caffeine (10 mg/kg of body weight, n = 4), ephedrine (5 mg/kg of body weight, n = 4), nicotine (0.8 mg/kg of body weight, n = 9), or a mixture of nicotine and ephedrine (0.8 mg/kg of body weight and 5 mg/kg of body weight, respectively, n = 9) was injected into the peritoneal cavity of female Lewis rats 30 min before intravenous (18)F-FDG injection. One hour after injection of (18)F-FDG, the animals were sacrificed, and BAT, other major organs, and blood were extracted. The biodistribution results were compared with body temperature data., Results: In the rats injected with nicotine or ephedrine, the mean uptake of (18)F-FDG, in percentage injected dose (%ID)/(g of interscapular BAT) x (kg of body weight), was significantly increased (7.9-fold for nicotine and 3.7-fold for ephedrine), compared to the control rats. Nicotine had the strongest effect on (18)F-FDG uptake in BAT. Caffeine increased BAT uptake slightly, but this increase did not reach statistical significance. The combination of nicotine and ephedrine increased the uptake 12.0-fold, compared with control rats; more than either nicotine or ephedrine alone. Uptake of (18)F-FDG in most other major organs did not change significantly. The effect of nicotine was blocked by prior injection of beta-adrenergic antagonists. A transient decrease in body temperature was observed in the nicotine-injected group, and this effect was canceled by prior injection of beta-adrenergic antagonists. No significant change in baseline temperature was seen before or after beta-adrenergic agonist injection., Conclusion: Nicotine caused a greater increase in (18)F-FDG uptake in BAT than did other interventions, and the effect was increased when nicotine was combined with ephedrine. The effect of nicotine was completely blocked by prior injection of beta-adrenergic antagonists, indicating that beta-adrenergic agonists increase the metabolism of BAT. These preclinical data suggest that patients should avoid nicotine and ephedrine before undergoing (18)F-FDG PET to minimize (18)F-FDG uptake in BAT.

It has been shown that vasoconstrictive drugs such as ephedrine derivatives are able to decrease systemic absorption of drugs administered by mucosal surfaces. The present paper set out to evaluate in the rat model the effect of co-administered nasal ephedrine on the absorption of GR138950 in a simple and in a pectin self-gelling formulation. It was hypothetised that a decrease in nasal systemic absorption would lead to an increase in direct nose-to-brain transport as demonstrated by the drug concentration in the olfactory lobes of the brain. It was found that ephedrine administered nasally with the drug in a simple aqueous solution resulted in a significant increase in nasal systemic absorption and also an increase in brain delivery; however, this trend was not observed with the pectin formulations. The pectin formulation with ephedrine resulted in lower systemic absorption of GR138950 and lower brain uptake compared to the simple solution formulation containing ephedrine.

Background: We previously found rostral spread of spinal plain levobupivacaine to be less with prophylactic i.v. phenylephrine than with ephedrine during Caesarean delivery. This study investigated whether rostral spread of spinal hyperbaric bupivacaine is also less with phenylephrine than with ephedrine., Methods: The study was randomized and double blind. It compared phenylephrine 100 microg ml-1 (phenylephrine group, n=27), and ephedrine 4.5 mg ml-1 (ephedrine group, n=27), given by infusion during spinal anaesthesia for Caesarean delivery. Block height was assessed to cold and light touch sensation at 15, 30, 60, and 90-min after the spinal injection of 2.8 ml of hyperbaric 0.5% w/v bupivacaine, combined with 0.4 ml diamorphine (1 mg ml-1). Umbilical blood gas values were monitored during the study., Results: Block height was similar for both groups at all of the assessment times. Umbilical artery pH was higher with phenylephrine [median 7.32 (IQR 7.28-7.34)] than with ephedrine [7.20 (7.10-7.28)] (P<0.0001). There was a strong negative correlation between umbilical artery pH and spinal-delivery interval, but only with ephedrine: phenylephrine group, r2=0.09 (P=0.17), and ephedrine group, r2=0.53 (P<0.0001). Five-minute Apgar scores were higher with phenylephrine [10 (9-10)] than ephedrine [9 (9-9)] (P=0.009)., Conclusions: In contrast to its effect on spinal plain levobupivacaine, we did not find rostral spread of spinal hyperbaric bupivacaine to be less with prophylactic phenylephrine than with ephedrine. We observed an unexpectedly high incidence of fetal acidosis with ephedrine and found evidence that longer spinal-delivery intervals increase the risk of fetal acidosis developing with ephedrine, but not phenylephrine.

Objective: The sympathetic nervous system and thiazolidinediones control lipid metabolism and have been implicated in body weight regulation. This study was conducted to determine whether the simultaneous activation of these two signaling systems might synergize to exert beneficial effects on the expression of key genes involved in lipid metabolism and mitochondrial biogenesis in subcutaneous fat in nondiabetic subjects., Research Design and Methods: A total of 57 women and men were randomized into four groups: 1) placebo/placebo (PP), 2) ephedrine HCl (25 mg, 3 times daily) plus caffeine (200 mg, 3 times daily)/placebo (ECP), 3) placebo/pioglitazone (45 mg) (PPio), and 4) ephedrine plus caffeine/pioglitazone (ECPio) for 16 weeks. Adipose tissue samples were obtained after 12 weeks of treatment to determine gene expression., Results: Body fat decreased by 6.0 and 4.6% in the ECP and ECPio groups, respectively, while remaining unchanged in the PPio and PP groups. Triglyceride levels decreased by -7.7, -24, -15.2, and -41 mg/dl after 16 weeks treatment in the PP, PPio, ECP, and ECPio groups, respectively. This indicates that pioglitazone groups with or without EC (ephedrine HCl plus caffeine) decreased triglycerides, and EC groups with or without pioglitazone decreased body weight. The mRNA for sirtuin 1 and CD36 increased only in the ECPio group. Carnitine palmitoyltransferase-1, medium-chain acyl CoA dehydrogenase, and malonyl-CoA decarboxylase increased with PPio and ECPio. Stearoyl-CoA desaturase decreased with ECP., Conclusions: Combined activation of peroxisome proliferator-activated receptor-gamma and beta-adrenergic receptors has beneficial effects on body weight, plasma triglycerides, and lipid metabolism in subcutaneous fat by increasing the expression of genes required for fatty acid catabolism.

A simple, rapid and accurate method for the separation and determination of paracetamol (Par), pseudoephedrine hydrochloride (Pse), dextromethorphan hydrobromide (Dex) and chlorphenamine hydrogen maleate (Chl) was developed by combination of flow injection and capillary zone electrophoresis for the first time. The analysis was carried out using an unmodified fused-silica capillary (75 mm x 75 microm i.d. x 375 microm o.d., effective separation length of 45 mm) and direct ultraviolet detection at 214 nm, 1.0 kV applied voltage. The optimized running buffer composed of 75 mM sodium borate-15% (v/v) acetonitrile (ACN) (pH* 9.30) was applied for the separation of the four analytes. The separation was achieved in 4.5 min. The sample throughput rate could reach up to 19 h(-1). The repeatability (defined as relative standard deviation) was 0.6%, 1.0%, 2.1%, 1.9% with peak height evaluation and 0.7%, 1.8%, 0.7%, 1.1% with peak area evaluation for Par, Pse, Dex and Chl, respectively. The limits of detection (S/N=3) were 0.22 microg/ml, 0.29 microg/ml, 0.42 microg/ml and 0.70 microg/ml for Par, Pse, Dex and Chl, respectively. The method was successfully applied to determine the four compounds in three cold medicines with recoveries in the range of 97.18-105.15%.

The physiologic variability of blood flow to the prostate has not been studied until this time. We report the vasoactive effects of sildenafil and phenylephrine on blood flow of the normal prostate. Sildenafil increases prostate blood flow by approximately 75% and phenylephrine reduces the flow incrementally. Administration of these drugs with dynamic contrast-enhanced magnetic resonance imaging may improve the diagnosis of cancerous tissue because according to the literature, tumor angiogenic vessels lack the vasoactive physiologic response of the normal tissue.

The global prevalence of obesity has increased considerably in the last decade. Tools for obesity management, including caffeine, ephedrine, capsaicin, and green tea have been proposed as strategies for weight loss and weight maintenance, since they may increase energy expenditure and have been proposed to counteract the decrease in metabolic rate that is present during weight loss. A combination of caffeine and ephedrine has shown to be effective in long-term weight management, likely due to different mechanisms that may operate synergistically, e.g., respectively inhibiting the phosphodiesterase-induced degradation of cAMP and enhancing the sympathetic release of catecholamines. However, adverse effects of ephedrine prevent the feasibility of this approach. Capsaicin has been shown to be effective, yet when it is used clinically it requires a strong compliance to a certain dosage, that has not been shown to be feasible yet. Also positive effects on body-weight management have been shown using green tea mixtures. Green tea, by containing both tea catechins and caffeine, may act through inhibition of catechol O-methyl-transferase, and inhibition of phosphodiesterase. Here, the mechanisms may also operate synergistically. In addition, tea catechins have antiangiogenic properties that may prevent development of overweight and obesity. Furthermore, the sympathetic nervous system is involved in the regulation of lipolysis, and the sympathetic innervation of white adipose tissue may play an important role in the regulation of total body fat in general.

Background and Purpose: Ephedrine and amphetamine can cause substantial increases in systemic arterial pressure. However, the role of endogenous noradrenaline release in mediating the pressor response to ephedrine is controversial. Studies using pharmacologic agents to decrease the synthesis, storage, and release of catecholamines have supported both a direct and an indirect mechanism of action for ephedrine. The purpose of the present study was to determine if endogenous noradrenaline release is required for cardiovascular responses to ephedrine and amphetamine using a genetic mouse model., Experimental Approach: Increases in systemic arterial pressure and heart rate in response to ephedrine and amphetamine were investigated and compared in dopamine beta-hydroxylase knockout (Dbh -/-) mice that cannot synthesize noradrenaline. Dbh +/- littermates have normal noradrenaline and adrenaline tissue levels, and served as controls in all experiments., Key Results: In Dbh -/- mice the increases in systemic arterial pressure and heart rate in response to i.v. injections of ephedrine were not impaired whereas responses to amphetamine were markedly reduced, when compared with responses in Dbh +/- mice. The pressor response to tyramine was abolished whereas pressor responses to noradrenaline, phenylephrine, dopamine, and angiotensin II were similar in Dbh -/- and Dbh +/- mice., Conclusions and Implications: The present results in Dbh -/- mice provide support for the hypothesis that pressor responses to ephedrine are directly mediated whereas responses to amphetamine are dependent on the release of noradrenaline and suggest that Dbh +/- and Dbh -/- mice are useful for the study of direct and indirect mechanisms.

Background: The noradrenergic system modulates cognitive flexibility for insight-based problem solving in studies using beta-adrenergic antagonists, which block noradrenergic neurotransmission postsynaptically. However, it is not known whether alpha2-adrenergic agonists, that decrease noradrenergic neurotransmission by presynaptic inhibition, have the same effect., Objectives: Therefore, we wished to test whether alpha2-adrenergic agonists would have a similar effect on cognitive flexibility., Methods: Eighteen normal adults were tested on cognitive flexibility, problem solving, verbal and spatial memory tasks after receiving clonidine (0.1 mg), an alpha2-agonist, placebo, or ephedrine (25 mg), a noradrenergic stimulant., Results: Three-way analysis of variance revealed no significant drug effect on cognitive flexibility or problem solving. There was also no significant effect of clonidine on memory., Conclusions: Therefore, alpha2-agonists do not influence cognitive flexibility in the same manner as beta-antagonists. Better performance on memory with clonidine might be expected based on primate studies demonstrating benefits in working memory using clonidine. This benefit was not observed for the commonly used clinical memory tasks in our study. This may have implications for why clonidine has not demonstrated efficacy for cognitive disorders such as Alzheimer disease, despite its known benefit for working memory in animal models.

Objective: To observe the effects of ephedrine on histomorphology and ultrastructure of nasal cavity mucosa from the healthy SD rats and explore the intervenient role of adenosine triphosphate(ATP)., Method: Twenty-three SD rats were divided randomly into three groups: Group A as control group; Group B for ephedrine; Group C for ephedrine and ATP (injection of ATP into peritoneal while ephedrine was given). Nasal cavity mucosa were taken for light microscopy (LM), transmission electron microscopy (TEM) at the 1st, 2nd, 3rd and 8th week of the experiment., Result: The damages in Group B of nasal cavity mucosa of the 1st, 2nd, 3rd week was aggravated gradually, histomorphology and ultrastructure of nasal cavity mucosa had no recovered after withdrawing drug until 8th week. Few damages in Group C of nasal cavity mucosa had been found in 1st week and a few damages were found in 2nd and 3rd week. The injured cells recovered definitely after stopping ephedrine and continuous application of ATP for another 5 weeks., Conclusion: The nasal cavity mucosa of SD rats can be damaged by ephedrine and the degree of damages of which becomes more serious with the increase of time. Furthermore the damages do not recover. ATP can alleviate the damages of nasal cavity mucosa from SD rats caused by ephedrine and prevent nasal cavity mucosa from the damages induced by ephedrine.

d-Pseudoephedrine (PSE) is one of the main ingredients of Ephedrae herba. Although PSE is widely applied for patients with a common cold and upper respiratory inflammation as a decongestant, the effects of PSE on cough have never been reported. In this study, we investigated the antitussive effects of intraperitoneal injection of PSE on the cough reflex induced by microinjection of citric acid into the larynx of guinea pigs. PSE decreased the number of cough reflexes dose-dependently (-18.3 +/- 5.0% at 20 mg/kg, P<0.05; -41.1 +/- 7.2% at 60 mg/kg, P<0.01). Furthermore, PSE (60 mg/kg) increased the threshold intensity for inducing fictive cough by electrical micro-stimulation of the nucleus tractus solitarius (+72.7 +/- 8.4%, P<0.01). On the afferent discharge of the superior laryngeal nerve, PSE suppressed the increases of amplitude and frequency when stimulated by citric acid at laryngeal mucosa. These results demonstrate that PSE possesses an antitussive effect that might be derived from both central and peripheral actions.

Objective: To investigate the effects of ephedrine on human nasal cilia movement., Methods: Ciliary beat frequency (CBF) of cultured human nasal epithelial cells was measured by high-speed digital microscopy in HBSS and ephedrine solution of different concentrations in 10 minutes., Results: CBF of cultured nasal epithelial cells exposed to HBSS showed no significant changes in 10 minutes. However, in 2.5 g/L , 5 g/L, 10 g/L and 20 g/L ephedrine solution, CBF increased significantly in 1-2 minutes and reached the apex, then it decreased gradually, at the 10th minute. CBF of the samples exposed to 2.5 g/L and 5 g/L ephedrine solution were slower than those in HBSS, but no significant changes were found. However, in 10 g/L and 20 g/L ephedrine solution, CBF decreased significantly when compared with samples in sHBSS. With the concentrations from 2.5 g/L to 20 g/L ephedrine, the increment was independent on the concentration, the inhibitory effect was dependent on the concentration., Conclusions: In initial time, 2. 5 g/L-20 g/L ephedrine stimulated CBF, then 10 g/L-20 g/L ephedrine inhibited CBF. The stimulation of 2.5 g/L and 5 g/L ephedrine on CBF was longer than that of 10 g/L and 20 g/L ephedrine. 5 g/L ephedrine had maximum stimulatory effect without obvious inhibitory effect on cultured human nasal CBF.

Pseudoephedrine is a sympathomimetic drug in which its structure is similar to amphetamine. Although pseudoephedrine is not as potent as amphetamine, it has been reported that the actions of pseudoephedrine on the central nervous system via dopamine release resemble to amphetamine. Changes of dopamine function can induce malfunction of glutamatergic system because there are well-documented interactions between glutamate/N-methyl-D-aspartate (NMDA) receptors and dopaminergic system. Therefore, the aim of this study was to investigate the effects of acute and chronic pseudoephedrine administration on NMDA receptors in hippocampal formation. Immunohistochemistry was used to determine the alteration of NMDA receptor density in rat hippocampus and dentate gyrus following acute and chronic pseudoephedrine administration. The density of NMDA receptors was increased significantly (p<0.005) in the dentate gyrus of animals treated with pseudoephedrine chronically when compared with the acute and control groups. Similarly, the density of NMDA receptors in an acute group was also higher than the control group (p<0.01). These results indicate that pseudoephedrine could induce an increase of NMDA receptors in the dentate gyrus. This might be a compensatory effect of NMDA receptor in response to the degeneration or loss of glutamatergic neurons.

Background and Objectives: Central nervous system (CNS) stimulants may be used to reduce tiredness and increase alertness, competitiveness, and aggression. They are more likely to be used in competition but may be used during training to increase the intensity of the training session. There are several potential dangers involving their misuse in contact sports. This paper reviews the three main CNS stimulants, ephedrine, amfetamine, and cocaine, in relation to misuse in sport., Methods: Description of the pharmacology, actions, and side effects of amfetamine, cocaine, and ephedrine., Results: CNS stimulants have psychotropic effects that may be perceived to be ergogenic. Some are prescription drugs, such as Ephedra alkaloids, and there are issues regarding their appropriate therapeutic use. Recently attention has been given to their widespread use by athletes, despite the lack of evidence regarding any ergogenic or real performance benefit, and their potentially serious side effects. Recreational drugs, some of which are illegal (cocaine, amfetamines), are commonly used by athletes and cause potential ergolytic effects. Overall, these drugs are important for their frequent use and mention in anti-doping laboratories statistics and the media, and their potentially serious adverse effects., Conclusions: Doping with CNS stimulants is a real public health problem and all sports authorities should participate in its prevention. Dissemination of information is essential to prevent doping in sport and to provide alternatives. Adequate training and education in this domain should be introduced.

Study Objectives: To evaluate the effects of clonidine and ephedrine on propofol-induced pain and on hemodynamic changes during the induction sequence., Design: This was a prospective, randomized, double-blind study., Setting: The study was conducted at a university hospital., Patients: 200 ASA physical status I or II adult patients scheduled for elective surgery., Interventions: Patients were randomly allocated to one of 4 groups (50 patients per group): clonidine-ephedrine (CE), clonidine-saline (CS), diazepam-ephedrine (DE), and diazepam-saline (DS). Thirty seconds after the administration of ephedrine or saline, propofol 2 mg/kg was infused at a rate of 18.3 mL/min., Measurements: Patients were asked whether they had pain due to propofol injection. A blinded investigator evaluated the pain score: 0 = no pain, 1 = mild pain, 2 = severe pain without behavioral signs such as grimace or arm withdrawal movement, and 3 = severe pain accompanied by behavioral signs. Mean arterial blood pressure (MAP) and heart rate (HR) were measured at 1-minute intervals from just before the administration of ephedrine or saline to 5 minutes after the tracheal intubation., Main Results: Median pain score in CE was significantly lower than those in the other groups (P < 0.0001). Pain scores in CS and DE were significantly lower than that in DS (P < 0.05). Ephedrine increased HR in CE and DE (P < 0.05), but clonidine did not augment the effect. Mean arterial blood pressure before tracheal intubation decreased to comparable values in all groups. After the intubation, mean arterial blood pressure and HR in CE and CS were significantly lower than those in DE and DS (P < 0.05)., Conclusions: Combination of clonidine and ephedrine effectively reduced propofol-induced pain, but did not prevent propofol-induced hypotension. Clonidine did not augment low dose of ephedrine-induced increase in HR and produced stable hemodynamic condition during the induction sequence.

Objective: To compare the urodynamic and hemodynamic effects of different dosages of phenylpropanolamine and ephedrine and determine effective dosages in increasing urethral resistance in female dogs., Animals: 20 sexually intact female Beagles., Procedure: Dogs were allocated into 4 groups and received phenylpropanolamine once, twice, or 3 times daily, or ephedrine twice daily, for 14 days. On days 0, 7, and 14, urethral pressure profiles were performed while dogs were anesthetized with propofol. Variables recorded included maximum urethral pressure, maximum urethral closure pressure, integrated pressure, functional profile length, anatomic profile length, plateau distance, distance before maximum urethral pressure, and maximum meatus pressure. Arterial and central venous pressures were measured before anesthetic induction and 10 and 35 minutes after induction., Results: Administration of phenylpropanolamine once daily or ephedrine twice daily significantly increased maximum urethral pressure and maximum urethral closure pressure. Values for integrated pressure were significantly increased after 14 days of once-daily administration of phenylpropanolamine. Variables did not change significantly from day 7 to day 14. Diastolic and mean arterial blood pressures increased significantly during the treatment periods, and arterial pressure decreased during propofol infusion., Conclusions and Clinical Relevance: Oral administration of phenylpropanolamine once daily or ephedrine twice daily increased urethral resistance in clinically normal dogs and may be recommended for management of urethral sphincter mechanism incompetence. Treatment efficacy may be assessed after 1 week. Dogs with concurrent cardiovascular disease should be monitored for blood pressure while receiving alpha-adrenergic agents because of the effects on diastolic and mean arterial pressure.

Akrinor (AKR), a mixture of theodrenaline (TDR) and cafedrine (CDR), is a sympathomimetic agent used to counter transitory hypotension. Although some cases of vascular complications associated with AKR have been reported there are no experimental data about its direct effects on coronary arteries. The effects of AKR, TDR, CDR, and ephedrine (EDR) were studied on the isometric contraction of the ring preparations of pig coronary arteries precontracted with KCl. The influence of endothelium removal and preincubation with nonselective beta-adrenoreceptor antagonist propranolol (PROP), alpha(1)-adrenoreceptor antagonist prazosin, dopamine receptor antagonist SCH 23390, and adenosine receptor antagonist CGS 15943 were also tested. AKR, TDR, and CDR produced relaxation of the preparations. Preparations without endothelium were more sensitive to AKR relaxing effects. EDR produced an increase of vascular ring tonus. AKR, TDR, and EDR produced contraction in preparations pretreated with PROP. Higher concentrations of AKR relaxed PROP-pretreated preparations. AKR-induced contraction could be prevented by pretreatment with prazosin. Dopamine and adenosine receptor antagonists did not influence relaxing effects of AKR. In conclusion, AKR and its constituents induce the relaxation of pig coronary artery preparations precontracted with KCl. The observed contraction in the preparations pretreated with PROP was probably due to stimulation of unmasked alpha(1)-adrenoreceptors.

The scale of the obesity epidemic creates a pressing consumer need as well as an enormous business opportunity for successful development and marketing of food products with added benefits for weight control. A number of proposed functional food ingredients have been shown to act post-absorptively to influence substrate utilization or thermogenesis. Characteristics and supporting data on conjugated linoleic acid, diglycerides, medium-chain triglycerides, green tea, ephedrine, caffeine, capsaicin and calcium, are reviewed here, giving examples of how these could act to alter energy expenditure or appetite control. Consideration is also given to other factors, in addition to efficacy, which must be satisfied to get such ingredients into foods. We conclude that, for each of the safe, putatively metabolically active agents, there remain gaps in clinical evidence or knowledge of mechanisms, which need to be addressed in order to specify the dietary conditions and food product compositions where these ingredients could be of most benefit for weight control.

As a contribution to the development of novel vanadyl complexes with potential insulin-mimetic activity, three new oxovanadium(IV) complexes with the formula VO(L)(2), where L are 3-amino-quinoxaline-2-carbonitrile N(1),N(4)-dioxide derivatives, have been synthesized. Complexes have been characterized by elemental and thermal analyses, fast atom bombardment mass spectroscopy (FAB-MS), conductivity measurements and electronic, Fourier transform infrared (FTIR) and electron paramagnetic resonance (EPR) spectroscopies. The in vitro insulin-mimetic activity of the vanadyl complexes has been estimated by lipolysis inhibition tests, in which the inhibition of the release of free fatty acid from isolated rat adipocytes treated with epinephrine was determined. All the complexes showed inhibitory effects on free fatty acid release. [V(IV)O(3-amino-6(7)-bromoquinoxaline-2-carbonitrile N(1),N(4)-dioxide)(2)] exhibited higher in vitro insulin-mimetic activity than the very active bis(6-methylpicolinato)oxovanadium(IV), VO(6mpa)(2). This new vanadyl complex is expected to exhibit a higher blood glucose lowering activity than VO(6mpa)(2) in diabetic animals.

Unlabelled: Pseudoephedrine is an over-the-counter drug to relieve nasal and sinus congestion. Although it has been suggested that pseudoephedrine could be a stimulant and ergogenic aid, pseudoephedrine was recently removed from the banned substance list by the International Olympic Committee and placed on the monitoring program (from January 2004). It was felt that evidence was lacking for an ergogenic effect, although few studies have investigated the effects of pseudoephedrine on exercise performance. This study, therefore, aimed to investigate the effects of pseudoephedrine on 1500-m running performance., Methods: In a double-blind, randomized crossover design, seven male athletes completed two 1500-m running trials on an outdoor track after having completed a familiarization trial. All trials were 7 d apart. After a 12-h overnight fast, subjects reported to the laboratory and received a standardized breakfast (energy asymptotically equal to 500 kcal 50% CHO). Subjects were given either 2.5 mg.kg(-1) bw pseudoephedrine or 2.5 mg.kg(-1) bw maltodextrins (placebo) in gelatin capsules 70 min before the start of the warm-up, which started 20 min before they ran 1500 m all-out. Pre- and postexercise blood samples were collected and analyzed for lactate and glucose concentrations, partial pressure of oxygen (PO2) and carbon dioxide (PCO2), and percent oxygen saturation., Results: Pseudoephedrine significantly decreased time to completion of 1500-m time trials in the present study by 2.1% (from 279.65 +/- 4.36 s with placebo to 273.86 +/- 4.36 s with pseudoephedrine) with no reported side effects. No changes in the measured blood parameters were found, suggesting a central effect of pseudoephedrine rather than a metabolic effect., Conclusion: The finding was that 2.5 mg.kg(-1) bw pseudoephedrine ingested 90 min preexercise improves 1500-m running performance.

Although ephedrine is a centrally active stimulant, its effect on midbrain dopamine neurons is not known. To study the effect of ephedrine on dopamine-containing cells, current-clamp microelectrode recordings were made from substantia nigra pars compacta (SNC) neurons in horizontal brain slice preparations. Ephedrine (100-1000 microM) slowed spontaneous firing and produced a modest concentration-dependent hyperpolarization of membrane potential (EC50 279 microM), with a concomitant net decrease in membrane resistance. These effects were blocked by the D2-like dopamine antagonist sulpiride (1 microM). Electrically evoked inhibitory synaptic potentials mediated by GABAB receptors were reduced 28% by ephedrine. However, ephedrine did not reduce fast synaptic potentials mediated by GABAA or ionotropic glutamate receptors. Inhibition of the GABAB response appeared to be mediated by a postsynaptic mechanism because ephedrine also reduced baclofen-induced hyperpolarization by 28%. Both ephedrine-induced hyperpolarization and inhibition of baclofen-induced hyperpolarization were abolished when slices were superfused with the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (AMPT). Despite perfusion with AMPT, the ability of ephedrine to cause hyperpolarization was restored after perfusing the slice with dopamine (30 microM). Taken together, these results suggest that ephedrine causes hyperpolarization and suppresses GABAB receptor-mediated effects by releasing endogenous dopamine. However, the high concentrations required to observe these effects in vitro suggest that biologically relevant central effects of ephedrine are more likely to be mediated either by non-dopamine systems, such as those involving noradrenaline, or by dopamine systems outside the SNC.

Current pharmacological regimens for hypertriglyceridemia and low high-density lipoprotein (HDL) are limited to the peroxisome proliferator-activated receptor (PPAR) alpha activating fibrates, niacin, and statins. This pilot study examined the impact of simultaneous stimulation of cyclic adenosine monophosphate with a beta-adrenergic agonist and PPARgamma with pioglitazone (PIO) on lipoprotein composition in moderately obese, healthy subjects. Subjects were treated with PIO (45 mg) to stimulate PPARgamma or a combination of ephedrine (25 mg TID), a beta-agonist, with caffeine (200 mg TID), a phosphodiesterase inhibitor (ephedrine plus caffeine), or both for 16 weeks. Lipoproteins were separated by gradient ultracentrifugation into very low-density lipoprotein (VLDL), intermediate-density lipoprotein, low-density lipoprotein (LDL), and 3 HDL (L, M, and D) subfractions. Apolipoproteins were measured by high-performance liquid chromatography. PIO alone reduced the core triglyceride (TG) content relative to cholesterol ester (CE) in VLDL (-40%), IDL (-25%), and HDL-M (-38%). Ephedrine plus caffeine alone reduced LDL CE (-13%), phospholipids (-9%), and apolipoprotein (apo) B (-13%); increased HDL-M LpA-I (HDL containing apoA-I without apoA-II, 28%), CE/TG (23%), and CE/apoA-I (8%) while reducing apoA-II (-10%); and increased HDL-L LpA-I (29%). Combination therapy reduced total plasma TG (-28%), LDL cholesterol (LDL-C, -10%), apoB (-16%), apoB/apoA-I ratio (-21%) while increasing HDL cholesterol (HDL-C, 21%), total plasma apoA-I (12%), LpA-I (43%), and apoC-I (26%). It also reduced VLDL total mass (-34%) and apoC-III (-39%), LDL CE (-13%), apoB (-13%), and total mass (-11%). Combination therapy increased HDL-L CE/TG (32%), apoC-I (30%), apoA-I (56%), and LpA-I (70%), as well as HDL-M CE (35%), phospholipids (24%), total mass (19%), apoC-I (25%), apoA-I (18%), and LpA-I (56%). In conclusion, simultaneous beta-adrenergic and PPARgamma activation produced beneficial effects on VLDL, LDL, HDL-L, and HDL-M. Perhaps the most important impact of combination therapy was dramatic increases in LpA-I and apoC-I in HDL-L and HDL-M, which were much greater than the sum of the monotherapies. Because LpA-I appears to be the most efficient mediator of reverse-cholesterol transport and a major negative risk factor for cardiovascular disease, this combination therapy may provide very effective treatment of atherosclerosis.