Search

Failure to thrive (FTT) impairs the expected normal physical growth of children. This study aimed to evaluate the effects of cyproheptadine hydrochloride on growth parameters in prepubertal children with FTT. The medical records of prepubertal children who were newly diagnosed with FTT at China Medical University Hospital between 2007 and 2016 were retrospectively examined. The patients were divided into two groups depending on whether they had (T-group) or had not (NT-group) received cyproheptadine hydrochloride (0.3 mg/kg daily) for at least 14 days. The mean length of the treatment period was 97.22 days (range: 14–532 days). Weight, height, and body mass index were adjusted for age using the median values in the growth charts for Taiwanese boys and girls as the reference. A total of 788 patients aged 3–11 years were enrolled, 50 in the T-group and 738 in the NT-group. No statistically significant difference in the median age-adjusted weight value was noted between the T-group and NT-group during the follow up period. In the T-group, age-adjusted weight and body mass index were inversely associated with age (P P P = 0.026, P = 0.04). Our findings underscore the positive association between cyproheptadine hydrochloride treatment and weight gain among prepubertal children. Further prospective clinical studies with a. longer and consistent treatment course is warranted.

Background The voltage-gated K+-channel Kv11.1 has a central role in cardiac repolarization. Blockage of Kv11.1 has been linked to severe cardiovascular side effects, such as acquired long QT syndrome (aLQTS), torsade de pointes arrhythmia and sudden cardiac death (SCD). Kv11.1 is susceptible to unspecific drug interactions due to the presence of two aromatic amino acids residing in the inner vestibule of the pore. These aromatic residues are also present in the equine orthologue of Kv11.1. This suggests that equine Kv11.1 may also be prone to high-affinity block by a range of different chemical entities, which potentially could cause severe cardiac side effects and SCD in horses. Aim To screen a series of commonly used drugs in equine medicine for interaction with Kv11.1. Methods High-throughput screening of selected compounds on human Kv11.1 expressed in a mammalian cell line was performed using an automated patch clamp system, the SyncroPatch 384PE (Nanion Technologies, Munich, Germany). Results were validated on equine Kv11.1 expressed in CHO-K1 cells by manual patch clamp. Results Acepromazine maleat (IC50 = 0.5 μM) trimethoprim (IC50 = 100 μM), diphenhydramine hydrochloride (IC50 = 2 μM) and cyproheptadine hydrochloride (IC50 = 1.84 μM) inhibited equine Kv11.1 current at clinically relevant drug concentrations. Conclusion The results suggest that drug interaction with Kv11.1 can occur in horses and that some drugs potentially may induce repolarization disorders in horses.

Cyproheptadine hydrochloride(CH)- and dexamethasone-induced obsessive-compulsive symptomatology with suicide is extremely rare. We describe the case of a 20-year-old lean male who developed obsessive-compulsive symptoms and suicidality within a week of the use of CH and dexamethasone. There was complete resolution of symptoms after stopping the offending agent. Ashort trial of selective serotonin reuptake inhibitor was given for the rapid improvement of symptoms.

Background: For the first time, the inhibitory effects on the human salivary alpha-amylase activity of the anti-inflammatory drugs indomethacin, diclofenac sodium, ketoprofen, diclofenac potassium, diclofenac, triamcinolone acetonide, and the antihistamine drugs levocetirizine dihydrochloride, desloratadine, cycloheptadine hydrochloride, have been investigated to confirm the other properties of these drugs. Objective: This study aimed to determine the effect of nine known drugs on human salivary α-amylase in vitro and the nature of interactions with structure-activity relationship using molecular docking experiments. Methods: The inhibition of human salivary alpha amylase by the six anti-inflammatory and three antihistamine drugs has been carried out using the new method that has been proved in our previous work. Molecular docking has been achieved for the first time for these drugs using the Auto- Dock Vina program. Results: Cyproheptadine hydrochloride presented the highest inhibitory activity against α-amylase with IC50=0.7 mg/ml, while the other drugs showed weak activities (IC50 > 2 mg/ml). Conclusion: We conclude that Cyproheptadine hydrochloride, which was studied by docking experiments, exhibited the best inhibitory activity on salivary α-amylase in vitro & in silico.

A sensitive, simple and rapid stability-indicating HPLC method using fluorescence detection was developed for the quantitative determination of the antihistaminic drug cyproheptadine hydrochloride ...

Topicality. Cyproheptadine hydrochloride (peritol) is an antihistaminic drug with an antiserotonin effect, which prevents development and facilitates the course of allergic reactions. The drug is characterized by antipruritic, antiexudative, anticholinergic and sedative effects. According to the literature sources, the drug can cause intoxication of the body and the lethal effects of overdosing, self-medication and in cases of suicide. The elaboration of highly sensitive and selective methods for the study of cyproheptadine, suitable for analysis in biological objects is an actual task. Aim. To study the elaboration of algorithm for the directed analysis of cyproheptadine in biological extracts by HPLC and TLC methods. Materials and methods. TLC studies were performed using 16 mobile solvent systems and three types of chromatographic plates. To identify the cyproheptadine were applied universally visualization conditions. HPLC studies were performed on a microcolumn liquid chromatograph “Milichrom A-02” (RPA “EkoNova” Novosibirsk, Russia) in a reversed-phase variant using a metal column with a non-polar sorbent Prontosil 120-5C 18 AQ. Results and discussion. TLC conditions for purifying cyproheptadine from biogenic impurities and its identification have been established. Based on the results of the studies, the behavior of cyproheptadine by the HPLC method was studied. Identification was carried out using retention parameters, spectral relationships, and quantitative determination using the absolute calibration method. The method is validated by parameters – range of linearity, limit of detection and quantitative determination, accuracy and precision. Conclusions. It was established that the most suitable TLC conditions for CTA of cyproheptadine are: mobile solvent systems – ethyl acetate-methanol-25 % solution ammonium hydroxide (85 : 10 : 5), glass plates of firm “Merk” ( Rf cyproheptadine = 0.50-0.55) and methanol, methanol-n-buthanol (60 : 40), Sorbphil-PTCX-AF-A ( Rf cyproheptadine = 0.55-0.58). It is established that the HPLC-method may determine cyproheptadine in a concentration range of 10.0-200.0 µg/ml. The relative uncertainty of the average result is ± 2.05 %. An algorithm for the direct analysis of cyproheptadine in biological extracts by HPLC and TLC methods has been developed.

Background: Cyproheptadine hydrochloride (HCl) is antihistaminic drug which used widely in our country as an appetizer and for weight gain especially for low weight children. Objective: The aims of this study were to assess the effects of cyproheptadine HCl on blood picture including white blood cells count, lymphocytes count, and its effect on the level of different cytokines. Materials And Methods: This is an experimental study conducted at Biotechnology Research Center Laboratory in Alnahrain University from November 2016 to April 2017. It included five groups of albino male mice, these groups were treated separately with four doses of the cyproheptadine drug and fifth as control group; the doses were selected according to the British National Formulary (BNF) 2010 calculated on the base of mice/human deference's in body weight: These are (0.065, 0.092, 0.120, 0.24) mg/mice/day, respectively, with fifth untreated mice group considered as control. Results: The untreated mice (control) lymphocyte count was (4000) cell/ml and the total lymphocytes count increased up to (7014) cell/ml than the normal leading changes in interleukins (ILs) level in different manner, such as decreasing in both IL-6 and IL-10 levels with increasing in IL-12 level and no change in IL-4 level. Conclusion: The current study showed that cyproheptadine HCl may have unwanted side effects, and its abuse may lead to disturbances in white blood cell especially lymphocyte which in turn will affect the immunity of persons taking it, especially in children, since the immune system modulates ILs secretion to face the irritability of drug behavior, that will lead abnormalities in human immune system.

Fluvoxamine is a selective serotonin-reuptake inhibitor, of which IC50 values for serotonin- and noradrenaline-uptake process were reported to be 3.8 and 620 nmol/L, respectively, also known to directly inhibit cardiac Na+, Ca2+, and K+ channels. We characterized microminipig as a laboratory animal by analyzing fluvoxamine-induced cardiovascular and dermatological responses under halothane anesthesia. Fluvoxamine maleate was infused in doses of 0.1, 1, and 10 mg/kg over 10 min with a pause of 20 min (n = 4). The peak plasma concentrations were 35, 320, and 1906 ng/mL, of which free plasma concentrations were estimated as 20, 187, and 1108 nmol/L, respectively. The low and middle doses did not alter any cardiovascular variable. The high dose increased heart rate and mean blood pressure, prolonged QRS width, but shortened QT interval, whereas no significant change was detected in PR interval or QTcF. Moreover, it induced systemic erythema on the skin. Pretreatment of H1/5-HT2A antagonist cyproheptadine hydrochloride sesquihydrate in a dose of 0.3 mg/kg significantly attenuated the fluvoxamine-induced pressor response; but tended to further enhance sinus automaticity, atrioventricular nodal conduction; and ventricular repolarization in addition to intraventricular conduction delay; whereas it markedly suppressed onset of systemic erythema (n = 4). In microminipigs, cardiovascular adverse effects of the high dose may be manifested as a sum of its inhibitory action on the cardiac ionic channels and its stimulatory effects on serotonergic and adrenergic systems, whereas dermatologic reaction can be induced primarily through H1/5-HT2A receptor-dependent mechanism. Thus, microminipigs may be used for analyzing such multifarious adverse events of clinical serotonergic pharmacotherapy.

Data available from the Dryad Digital Repository: < http://dx.doi.org/10.5061/dryad.768vg > (Martín-Gálvez and Soler 2016), The colouration of some traits in nestlings of altricial birds may influence parental food allocation as it may reflect physical condition or hunger. There is increasing evidence of the relationship between colouration of begging traits and nestling performance. However, evidence of the influence of hunger level on nestling colouration is scarce, mainly because of difficulty of distinguishing between the effects of physical condition and hunger levels. Here, we used the appetite stimulant cyproheptadine hydrochloride to increase the sensation of hunger of magpie Pica pica nestlings for eight days and assessed the effect on the colouration of rictal flanges, mouth and body skin. We found that nestlings administered with cyproheptadine had flanges more conspicuous (chromatic visual contrast), more UV coloured and less yellow coloured than their control nestmates. Conversely, mouths of experimental nestlings were more yellow coloured and less UV coloured than controls. Our pharmacological experiment afected the strength of the relationship between body mass and some colour components of body skin (chromatic and achromatic visual contrasts, UV – chroma and yellow – chroma) and of rictal flanges (chromatic visual contrasts, UV – chroma and yellow – chroma), but not for mouth colouration. These results taken together suggest that the effect of the cyproheptadine on nestling colourations is probably mediated by an increase in hunger levels of nestlings for rictal flanges and body skin colourations, and by an increase in physical condition in the case of mouth coloration., Th is research was funded by a postdoctoral fellowship to DM-G from Ministerio de Educación y Ciencia, and by Ministerio de Ciencia e Innovación/FEDER (project CGL2013-48193-C3-1-P)

The interaction between cyproheptadine hydrochloride (CYP) and human serum albumin (HSA) was investigated by fluorescence spectroscopy, UV-vis absorption spectroscopy, Fourier transform infrared spectroscopy (FT-IR) and molecular modeling at a physiological pH (7.40). Fluorescence of HSA was quenched remarkably by CYP and the quenching mechanism was considered as static quenching since it formed a complex. The association constants Ka and number of binding sites n were calculated at different temperatures. According to Förster's theory of non-radiation energy transfer, the distance r between donor (human serum albumin) and acceptor (cyproheptadine hydrochloride) was obtained. The effect of common ions on the binding constant was also investigated. The effect of CYP on the conformation of HSA was analyzed using FT-IR, synchronous fluorescence spectroscopy and 3D fluorescence spectra. The thermodynamic parameters ΔH and ΔS were calculated to be -14.37 kJ mol(-1) and 38.03 J mol(-1) K(-1), respectively, which suggested that hydrophobic forces played a major role in stabilizing the HSA-CYP complex. In addition, examination of molecular modeling indicated that CYP could bind to site I of HSA and that hydrophobic interaction was the major acting force, which was in agreement with binding mode studies.

Appetite stimulants have been used to help overcome decreased appetite and malnutrition in children and adults with various chronic illnesses, including cystic fibrosis (CF). Stimulants have included megestrol acetate (MA), cyproheptadine hydrochloride (CH), cannabinoids, hydrazine sulfate, anabolic hormones, and growth hormone. Many of these, including MA, have substantial side effects and may not be suitable for prolonged use. We previously studied the effects of CH on weight gain in a short-term (12 week) trial in CF with good results compared to placebo. Side effects were few, and weight gain was significant. In this study, we sought to determine the effects of CH over a longer term in order to assess its suitability for prolonged use. Sixteen CF children and adults enrolled in the original short-term study subsequently entered this study, and 12 completed the 9-month trial. All patients receiving placebo in the original short-term study received CH 4 mg up to four times a day in the long-term study continuation, and those receiving CH in the short-term study continued on the drug. No pill counts were done, and patients were queried at quarterly visits as to their CH use. Anthropometrics and spirometry were also done quarterly, and antibiotic use was quantified. Subjects who had changed from placebo (CH2 group) gained weight significantly over 3-6 months, and those continuing on CH (CH1 group) generally maintained previously gained weight over the duration of the study. Select spirometric measures improved in both groups but not significantly, and side effects were mild. CH appears to be an effective appetite stimulant in CF, and generally maintains its effect over time with an acceptable side-effect profile.

Cyproheptadine hydrochloride (C) shows an antihistaminic as well as antimuscarine, antiserotonic and sedative activity. The present work describes sensitive and reasonably selective poly(vinyl chloride) membrane electrodes for Cyproheptadine. They are based on the use of cyproheptadine-tetrakis(4-chlorophenyl)borate (C-TC1PB) and cyproheptadine-dipicrylamine (C-DPA) as a novel electroactive compound. Cyproheptadine ion-selective poly(vinyl chloride) membrane electrodes contain an ion-pair complex of Cyproheptadine with 2-nitrophenyloctyl ether (ENPO), 2-nitrodiphenyl ether (ENdP), bis(2-ethylhexyl)sebacate (DOS) and l-isopropyl-4-nitrobenzene (IPNB) as solvent mediators. The performance of the electrodes was investigated by measuring the e.m.f. values of 10 −2 –10 −7 mol 1 −1 Cyproheptadine hydrochloride. The effect of pH on the potential readings of the Cyproheptadine electrodes was checked by the recording on the e.m.f. of 10 −3 mol 1 −1 Cyproheptadine hydrochloride with pH values from 2.5 to 7.0. Potentiometric selectivity coefficient were measured by the separate solution method using a 10 −3 mol 1 −1 concentration of Cyproheptadine and the some concentration of interferent cations. The electrode obtained with C-TC1PB with DOS and electrode with C-DPA with IpNB were used in the potentiometric determination of Cyproheptadine in bulk substance and tablets PERITOL 4 mg as indicator electrodes. The results are in good agreement with those obtained by UV spectrophotometric method. Keywords: Cyproheptadine hydrochloride; Ion-selective electrode; Potentiometric titration; Cyproheptadine determination; Drag analysis

The British Pharmacopoeia (BP) monograph for cyproheptadine HCl tablets requires a ‘Related substances’ thin-layer chromatography (TLC) test. This test revealed an extraneous spot with an R f of 0.1 in certain cyproheptadine HCl tablets that were under ambient retention conditions as well as those on stability programs. An investigation utilizing LC-MS, direct infusion MS, NMR, and organic synthesis has identified that the spot results from the N -oxide of cyproheptadine (a genuine degradate) and a co-eluting cyproheptadine–dichloromethane adduct, an artifact formed during the sample extraction step in which dichloromethane is used in the extracting solvent.

Cyproheptadine hydrochloride (CH) is rarely used to treat adult patients with migraine in Japan because it causes sleepiness. In this study, we investigated the preventive effect of CH in 12 patients who had failed to respond to conventional preventive treatments among 103 migraine patients treated at our hospital. These 12 subjects had all received unsuccessful migraine prophylaxis with lomerizine, valproic acid and topiramate, or had discontinued these treatments due to adverse reactions. Initially, the subjects were given 4 mg CH before sleeping. In those who experienced no clinically significant sleepiness following the treatment, the drug was orally administered at 4 mg after breakfast as well (8 mg per day in total). Drug efficacy was evaluated by examining the frequency of migraine at one month and three months after the start of treatment. The frequency of migraine was dramatically reduced in all patients within 7 to 10 days after starting treatment. The average frequency of migraine during the three-month period was 2.6 episodes per month, representing a significant (p

1. Metabolites formed during incubation of the antihistamine cyproheptadine hydrochloride with the zygomycete fungus Cunninghamella elegans in liquid culture were determined. The metabolites were isolated by hple and identified by mass spectrometric and proton nmr spectroscopic analysis. Two C elegans strains, ATCC 9245 and ATCC 36112, were screened and both produced essentially identical metabolites. 2. Within 72 h cyproheptadine was extensively biotransformed to at least eight oxidative phase-I metabolites primarily via aromatic hydroxylation metabolic pathways. Cyproheptadine was biotransformed predominantly to 2-hydroxycyproheptadine. Other metabolites identified were 1- and 3-hydroxycyproheptadine, cyproheptadine 10,11-epoxide, N-desmethylcyproheptadine, N-desmethyl-2-hydroxycyproheptadine, cyproheptadine N-oxide, and 2-hydroxycyproheptadine N-oxide. Although a minor fungal metabolite, cyproheptadine 10,11-epoxide represents the first stable epoxide isolated from the microbial biotransformation of drugs. 3. The enzymatic mechanism for the formation of the major fungal metabolite, 2-hydroxycyproheptadine, was investigated. The oxygen atom was derived from molecular oxygen as determined from 18O-labelling experiments. The formation of 2-hydroxycyproheptadine was inhibited 35, 70 and 97% by cytochrome P450 inhibitors metyrapone, proadifen and 1-aminobenzotriazole respectively. Cytochrome P450 was detected in the microsomal fractions of C. elegans. In addition, 2-hydroxylase activity was found in cell-free extracts of C. elegans. This activity was inhibited by proadifen and CO, and was inducible by naphthalene. These results are consistent with the fungal epoxidation and hydroxylation reactions being catalysed by cytochrome P450 monooxygenases. 4. The effects of types of media on the biotransformation of cyproheptadine were investigated. It appears that the glucose level significantly affects the biotransformation rates of cyproheptadine; however it did not change the relative ratios between metabolites produced.

Importance We describe a case of serotonin syndrome secondary to clozapine withdrawal and concomitant use of citalopram hydrobromide, a phenomenon that has been rarely reported. Observations This is a case report of a 47-year-old woman admitted to an academic medical center intensive care unit with coma, hypersalivation, hyperreflexia, and stimulus-induced clonus. The patient received a diagnosis of serotonin syndrome attributed to abrupt clozapine withdrawal with concomitant use of citalopram. She improved only minimally with supportive treatment (intravenous fluids, benzodiazapines, and withdrawal of selective serotonin-reuptake inhibitor) and received cyproheptadine hydrochloride on her third day of symptoms. Four hours after she received the loading dose of cyproheptadine, she was alert and oriented and at her baseline mental status, although some clonus remained. Conclusions and Relevance Serotonin syndrome can result from the abrupt withdrawal of a 5-hydroxytryptamine receptor 2A antagonist from a treatment regimen that also includes a medication that increases serotonin availability.

The reaction between haematoxylin reagent and eight antihistaminic drugs (chlorpheniramine maleate, pheniramine maleate, cyproheptadine hydrochloride; astemizole, terfenadine, ranitidine hydrochloride, famotidine and cimitidine) was investigated and utilized as the basis for a new, simple and sensitive spectrophotometric procedure for their determinations. The procedure is based on the reaction of the methanolic solution of the anti-histaminic compounds with haematoxylin reagent in 3x10-3 M boric acid to give a reddish-violet colour (lmax 555 nm). The absorbance was linear with all compounds over the 5-200 µg/ml general concentration range of the final measured antihistamine base solution. A good correlation was found between log A (1%, 1 cm) and pka values for six of the studied drugs. The method can be applied successfully to the analysis of commercially available tablet formulations. No interference was observed due to additives which are commonly present in tablet formulations or coformulated compounds such as phenazone, phenazone salicylate, sodium salicylate paracetamol, propyphenazone and caffeine.

Purpose: To evaluate the effect of formulation variables on the bioadhesion and release properties of bioadhesive cyproheptadine hydrochloride tablets. Methods: Screening of polymers - hydroxypropyl methylcellulose, (HPMC), sodium carboxy methyl cellulose (CMC), and Carbopol 974p and 934p - in solution form were carried out by shear stress and detachment force measurement,based on Taguchi model, in order to determine their bioadhesion properties. Central composite design (CCD) was applied to optimize the combined effects of the polymers on release rate constant (K), diffusion coefficient (n), regression coefficient (R 2 ) and detachment force of a sustained release tablet formulation of cyproheptadine hydrochloride containing also a prompt dose of the drug. Results: The shear stress of 3 % solution of HPMC was greater than that of an equivalent concentration of Carbopol 934P. The values of K, n, R 2 and detachment force for the optimized formulation (F0) were 0.269, 0.696, 0.964 and 0.066 Newton (N), respectively, and showed good correlation with the predicted values, thus confirming the practicability and validity of the model. Conclusion: Gastric retention time can be increased for cyproheptadine hydrochloride by formulating it as a bioadhesive tablet that enhances the retention of the dosage form in the stomach and hence gastric absorption of the drug. Keywords: Cyproheptadine hydrochloride, Bioadhesive core tablet, Detachment force, Taguchi design, Central composite design

We investigated the effects of several agents on the established itching model in NC/Nga mice, model of atopic dermatitis-like disease, to elucidate related characteristics. The number of spontaneous scratching behaviors (the duration time is over 1.5 s) by NC/Nga mice with severe skin lesions was measured before and after administration of agents for 24 h. The scratching behavior by NC/Nga mice was significantly suppressed by administration of dexamethasone or tacrolimus, but not by chlorpheniramine maleate or cyproheptadine hydrochloride. These results suggest that this method shows a good correlation with the effectiveness of drugs prescribed for itching in humans with atopic dermatitis, and histamine and serotonin do not play an important role in causing the scratching behavior seen by NC/Nga mice. The scratching behavior was also significantly suppressed by naloxone hydrochloride, dibucaine or capsaicin. These results suggest that the scratching behavior seen in this model is caused by itching signal transmission through neural system. Furthermore, we found that theophylline, pinacidil or limaprost had scratching suppression effects in this model.

Cyproheptadine (CY) has been used therapeutically as an appetite stimulant at a dose which appears to have antiserotoninergic activity. However, the role which CY may play in appetite regulation remains unclear. This study was designed to examine the effect of CY on ingestive behaviours in female Wistar rats. CY administered orally (0.52 mg kg-1 b.w., dissolved in the daily water) for up to six oestrus cycles did not affect 24 h food intake. On the other hand, CY reduced both 24 h liquid intake and 24 h urine output. Furthermore, 24 h liquid consumption and 24 h urine output, were found to fluctuate according to the oestrus cycle. Pharmacol Res

The inherent blood schizontocidal activities of five antihistaminic compounds, cyproheptadine hydrochloride (CYP), ketotifen hydrogen fumarate (KET), pizotyline hydrogen maleate (PIZ), azatadine maleate (AZAT) and loratadine (LOR) were examined against the following organisms: chloroquine-sensitive (CS) Plasmodium berghei and chloroquine-resistant (CR) P. yoelii ssp. NS in mice; and CS Tak 9 clone 96 and CR K1 strain of P. falciparum in vitro. Chloroquine, verapamil and desipramine were used as comparison standards. CYP, KET, PIZ were active against the CS strain in vivo with ED90 levels between 20 and 30 mg kg-1 (given sc daily for four days). They were slightly more active against the CR strain. AZA was active, but much less so than the other compounds. LOR, verapamil and desipramine were inactive in vivo at the doses tested. Against CS P. falciparum in vitro, all five antihistaminics and desipramine were active at EC50 concentrations ranging from about 50-80 mumol l-1, while verapamil was only active at 175 mumol l-1. Against the CR strain of this parasite, CYP, PIZ and LOR were slightly more active than against the CS strain, but KET, AZAT, desipramine and verapamil were significantly less active. The action of all these compounds in combination with chloroquine was then examined both in vivo and in vitro. The ability of verapamil and desipramine to reverse chloroquine resistance in vitro was confirmed, but only a low level of reversal was seen with these compounds in vivo. However, CYP, KET, PIZ and AZAT produced a marked reversal of chloroquine resistance both in vivo and in vitro. The implications of these observations in relation to further laboratory and clinical research are discussed.

Erythromelalgia is a rare disorder characterized by burning pain of the extremities associated with red discoloration and increased temperature of the skin. We observed the effects of several drugs on two patients with primary erythromelalgia. Anti-inflammatory drugs such as aspirin had no effects for their symptoms. The alpha-adrenergic agonist midodrine slightly reduced skin temperature and redness of the extremities, and minimally reduced the pain in one patient. The partial alpha-adrenergic agonist and 5-hydroxytryptamine (5-HT) agonist/antagonist dihydroergotamine transiently reduced skin temperature and pain to some degree in one patient. The 5-HT and histamine antagonist cyproheptadine effectively relieved the burning pain and increased skin temperature.

The clinical features and risk of hepatotoxicity of ‘Sleep-Qik’ (valerian dry extract 75 mg, hyoscine hydrobromide 0.25 mg, cyproheptadine hydrochloride 2 mg) were determined in 23 patients treated in our hospital between 1988 and 1991. The main clinical problems were central nervous system depression and anticholinergic poisoning. There was no clinical evidence of acute hepatitis in the 23 patients after taking an average of 2.5 g of valerian (range 0.5 to 12 g). There was no evidence of subclinical liver damage in 12 patients who had routine liver function tests performed approximately 6-12 hours after ingestion. Delayed onset of severe liver damage was excluded in 10 patients in whom a telephone follow-up was possible. However, subclinical liver dysfunction in the acute stage (onset after 12-24 hours) and in the intervening period after discharge from hospital could not be excluded. To establish the risk of hepatotoxicity in long-term users and in those taking an overdosage of valerian, a much larger study of longer duration with serial liver function tests is clearly needed.

Epidermolysis bullosa simplex—Dowling-Meara (EBS-DM) is a severe form of EBS, with oral and nail involvement as well as severe skin blistering. Reports1,2of treatment with 5-hydroxytryptamine—2 antagonists reducing the severity of blisters in subjects with EBS-DM prompted us to study cyproheptadine hydrochloride therapy in 13 individuals with a diagnosis of EBS-DM confirmed by electron microscopic examination. Participants served as their own controls. There was a 2-week observational period, an initial 6-week period during which cyproheptadine was taken daily, a 4-week period with no treatment, and a second 6-week regimen of daily administration of cyproheptadine. Standard dosages of cyproheptadine were used.3The study was designed in this manner in an attempt to compensate for temporal variation in blister formation as well as variations in season, weather, and activity levels of the participants. Subjects were asked to record the number of blisters lanced each day rather than the

The mechanism of hypotension induced by petroleum ether seed extract of Croton penduliflorus (PEE-CP) was investigated in pentobarbital-anesthetized dogs and was compared with that of an official sample of Croton tiglium (PEE-CT). Prior treatment of the animals with mepyramine maleate and cyproheptadine hydrochloride did not modify the hypotensive activity of these extracts indicating the absence of histaminergic and serotoninergic mechanisms in the responses. When the animals were pretreated with atropine sulfate, the fall in blood pressure produced by intravenous injections of PEE-CP and PEE-CT was significantly decreased. Similarly, the PEE-CP and PEE-CT inhibited the responses to isoproterenol sulfate, a beta-adrenergic stimulant. In addition, propranolol hydrochloride effectively augmented the depressor effects of the seed extracts. The hypotensive effects of PEE-CP closely resembled those of PEE-CT. It is concluded that the hypotension produced by the seed extracts of Croton penduliflorus is...

In order to clarify the effects of cyproheptadine hydrochloride (Cyp) which is known clinically to stimulate the appetite and a subsequent increase in body weight, acute and chronic experiments were carried out. In the acute experiments, changes in single neuronal activity in the lateral area (LH) and ventromedial nucleus (VMH) in the rat hypothalamus by applications of Cyp, Na and Cl were studied by means of multibarreled electrodes. (1) About 60% of the VMH neurons were reduced in firing frequency by Cyp. Most of them were increased in frequency by glucose. (2) About 70% of the LH neurons were increased in frequency by Cyp. However, most of them were inihibited by glucose. (3) The activity of the Cyp sensitive neurons was modulated by stimulations of either the basolateral amygdaloid nucleus of the stria terminalis. (4) In the chronic experiments, food intake and body weight in young rats were significantly increased by Cyp. Thus, it was concluded that Cyp modulates both LH and VMH neurons which might account for its effects on feeding in children.

A 13-year-old female ingested an acute overdose of cyproheptadine hydrochloride (Periactin) and presented for treatment. She manifested all the classic signs and symptoms of an acute antihistamine overdose, including psychosis, except for miotic, minimally reactive pupils. The patient was supportively managed. All sequelae of the ingestion resolved within four days, and the child was released from the hospital. We discuss the unusual presentation of miotic pupils in an acute cyproheptadine overdose.

The effect of Periactin® on the rejection course was examined in 36 kidney allograft recipients. Half of the patients were given 32 mg of Periactin® daily as a supplement to the immunosuppressive treatment consisting of prednisone and azathioprine. The other half was given only the latter two medicaments. Rejection crises were treated with intravenous infusion with methylprednisolone. No beneficial effect of the Periactin® treatment was demonstrable. Graft survival and kidney functions thus did not differ between the two groups within the first 90 days after the transplantation. The frequency of rejection, on the other hand, was significantly higher in the group treated with Periactin®, especially within the first postoperative week. Periactin®, apparently, does not offer any advantage as a supplement to the immuno-suppressive treatment in human kidney transplantation.

Infusions of serotonin into a rat nervemuscle preparation decreased the force of the evoked twitch of anterior tibial and soleus muscles. Antiserotonin drugs (cyproheptadine hydrochloride, methysergide, chlorpromazine hydrochloride) prevented the adverse effect of serotonin if they were given prior to the serotonin infusion. These experiments support the hypothesis that serotonin may play a role in some diseases of muscle.

SUMMARY The effect of cyproheptadine hydrochloride on release of prolactin (PRL), growth hormone (GH) and cortisol following insulin-induced hypoglycaemia was investigated in a group of eight adult female and male subjects. The results of this study demonstrated that cyproheptadine does not influence the release of these three hormones under the conditions employed in this study. The conflicting observation concerning the action of cyproheptadine on pituitary function as reported in the literature, may be a reflection of the diversity of pharmacological actions of this drug. Thus, any purported influence this drug might have on pituitary hormonal release should be interpreted with caution.

• Patients with anorexia nervosa have concurrent problems of emaciation and depression. Therefore, treatment with medications affecting both weight gain and depression seemed reasonable. Seventy-two anorectic patients were randomly assigned in a double-blind study to receive cyproheptadine hydrochloride, a weight-inducing drug, amitriptyline hydrochloride, a tricyclic antidepressant, or placebo. Overall, cyproheptadine had a marginal effect on decreasing the number of days necessary to achieve a normal weight. There was a differential drug effect present in the bulimic subgroups of the anorectic patients: cyproheptadine significantly increased treatment efficiency for the nonbulimic patients and significantly impaired treatment efficiency for the bulimic patients when compared with the amitriptyline- and placebo-treated groups. The differential cyproheptadine effect on the anorectic bulimic subgroups is the first pharmacologic evidence of the validity of these subgroups. Cyproheptadine had an antidepressant effect demonstrated by a significant decrease in the Hamilton depression ratings.

A reversed passive Arthus reaction was produced in guinea-pig knee joints by intravenous injection of ovalbumin and intra-articular injection of homologous anti-ovalbumin antiserum or specific IgG2 antibody. The optimum response was obtained by varying the concentration of antigen while keeping the amount of antibody constant. Joint swelling, leucocyte infiltration in the synovial fluid and joint pathology were measured 4–6 hours and 24 hours after initiation of the reaction. The PRA lesions were almost completely inhibited by complement or polymorphonuclear leucocyte depletion. The effects of a range of drugs on the 4–6 hours response were investigated following intraperitoneal or oral administration. Cyproheptadine hydrochloride, Trasylol, indomethacin, aspirin, phenylbutazone, prednisolone sodium phosphate, chloroquine diphosphate, SKF36914 (gold triethyl phosphine), cyclophosphamide, ketoprofen, sudoxicam and naproxen all reduced one or more of the symptoms of inflammation. However, cyproheptadine was only active at high and probably non-specific dose levels. D(−)penicillamine hydrochloride and mepyramine maleate were inactive.

Publisher Summary This chapter discusses a study to investigate the effect of trazodone and its metabolite, m-chlorophenylpiperazine (CPP), on acquisition of conditioned avoidance response. Male CD-1 mice were trained for conditioned avoidance response (CAR) in a shuttle-box apparatus. Each group consisted of 8 mice. The training comprised of 5 daily sessions of 100 trials each. CPP, 2 or 5 mg/kg (hydrochloride), was given 30 min before each session. Before CPP, the following drugs were given at times as indicated: cyproheptadine hydrochloride (CHD) 0.5 or 1 mg/kg, 30 min; alpha-methyl-p-tyrosine (AMT) 100 mg/kg, 90 min; pimozide (PMZ) 0.2 mg/kg, 60 min. All drugs were dissolved in 0.9% NaCl solution (saline), with the exception of PMZ, which was dissolved in 0.2% tartaric acid (vehicle). The controls received the solvent (10 ml/kg) at appropriate time intervals. All injections were given intraperitoneally. It was found that CHD did not antagonize the facilitatory action of CPP and in a dose of 1 mg/kg facilitated the CAR acquisition by itself. The effects of CPP and CHD were not additive.

Exposure of rat uterine horn suspended in de Jalon's solution, to Cyproheptadine hydrochloride (Cy) (10 μg/ml) inhibited response to prostaglandin E2 (20 ng/ml). The inhibition persisted even after removal of CY from the bath. Inhibition of response to E2 & F2α could be reversed by addition of calcium chloride to the bath. The extent of reversal was dependent on the concentration of calcium chloride. CY (10 μg/ml) completely inhibited contractile response to potassium free de Jalon's solution and partially inhibited cold contracture. These inhibitory actions could be reversed by addition of calcium chloride. CY was found to be a non-competitive antagonist of calcium. It is concluded that antagonism of CY to prostaglandins is due to its interference with entry of calcium into cytoplasm.

• Twenty-four-hour measurements of wrist and ankle kinetic energy expenditures were obtained on 20 hospitalized female anorectics during the first two weeks of their hospitalization. Kinetic energy was examined against measures of weight, depression, and Minnesota Multiphasic Personality Inventory scores in a regression analysis. Effect of cyproheptadine hydrochloride, amitriptyline hydrochloride, and placebo on activity was assessed. The results supported previous studies showing a positive relationship between weight gain and motor activity and challenge the commonly held notion that activity decreases in anorectics as their clinical condition improves. Motor activity was initially significantly suppressed by cyproheptadine and subsequently increased.

To the Editor.— In an earlier publication 1 we reported the effects of cyproheptadine hydrochloride on weight gain in 81 anorexia nervosa patients. Cyproheptadine is a serotonin and histamine antagonist with anticholinergic and sedative effects. Since that time, we have completed the full sample of 105 patients and have found that cyproheptadine affects characteristics of anorexia nervosa other than body weight. Females aged 10 to 40 years who met our study criteria for anorexia nervosa (an adaptation of those of Feighner et al 2 ) were entered into a pretreatment period of seven days in hospital, after which they were randomly allocated to groups receiving combinations of (1) cyproheptadine or placebo, and (2) behavior modification or its absence, and followed up on these treatments in the hospital for 35 days. Aside from body weight, patients were evaluated periodically on a variety of symptoms, behaviors, and attitudes. This design was repeated in

Administration of cyproheptadine hydrochloride (5 mg/kg/day) to old rats for 48 days stimulated spermatogenesis. It also initiated spermatogenesis in the abdominal testis of unilaterally cryptorchid rats after a 15-day treatment.

• The addition of orally administered bromocriptine mesylate to cyproheptadine hydrochloride therapy completely normalized urinary-free cortisol levels for three months in a 21year-old woman with Cushing's syndrome in whom results from standard dexamethasone suppression and metyrapone stimulation tests as well as baseline corticotropin levels were originally compatible with a diagnosis of an occult pituitary adenoma. When transsphenoidal exploration of the sella turcica was unsuccessful and hypercortisolism persisted, the source of corticotropin was discovered using petrosal sinus and venal caval catheterization. A1 × 1.5-cm carcinoid tumor of the lung was identified and removed, thereby correcting the hypercortisolism. The tumor was demonstrated by immunoperoxidase staining to contain corticotropin. Orally administered bromocriptine, with or without cyproheptadine therapy, may be useful in the palliative treatment of some patients with carcinoid or other ectopic corticotropin-producing tumors. We postulate that bromocriptine therapy acted directly on carcinoid tumor cells to directly inhibit corticotropin production by a dopaminergic mechanism. ( Arch Intern Med 1987;147:989-991)

Sir. —It is well known that cyproheptadine hydrochloride (an antihistamine with serotonin-antagonistic activity) has an appetite-stimulating effect and promotes weight gain. 1, 2 However, its effect in promoting linear growth in association with weight gain often seems to be overlooked although it has been documented. 3-5 We therefore wish to report our observations during 29 months of cyproheptadine administration in a small-for-gestational-age female infant to reemphasize the usefulness of this low-cost drug therapy for growth enhancement. Patient Report. —A 4-year-old girl had been born normally to a 28-year-old woman after a 40-week gestational period. The infant's birth weight had been 2.32 kg ( At the age of 1

• Eight subjects with primary-acquired cold urticaria were treated with chlorpheniramine maleate, cyproheptadine hydrochloride, and placebo in a double-blind clinical trial. During three separate seven-day treatment periods, each patient took 4 mg of either active drug or lactose placebo three times a day. Objective measurements were made at the beginning and end of each treatment period by establishing the minimum time (MT) of cold stimulus application required to provoke urtication. In addition, the spontaneous appearance of cold urticaria lesions was recorded during each treatment period. The MT required for induction of urtication with a cold stimulus was significantly greater for eight patients receiving cyproheptadine as compared to chlorpheniramine or placebo (P ( Arch Dermatol 113:1375-1377, 1977)

CUSHING'S syndrome is usually treated surgically when it is associated with pituitary-dependent adrenocortical hyperplasia or an adrenal adenoma. However, the patient's general condition may exclude a surgical approach, and in these cases as well as in certain instances of Cushing's syndrome due to metastatic adrenal carcinoma of ectopic adrenocorticotropic hormone (ACTH) production, medical treatment has a place. The drugs available include mitotane, aminoglutethimide, and metyrapone; more recently, successful treatment of adrenocortical hyperplasia with cyproheptadine hydrochloride has been reported. Mitotane and aminoglutethimide have been the most commonly used, but both have a high incidence of adverse reactions. 1 Only mitotane leads to permanent destruction of the adrenal cortex. Spironolactone is commonly used in the management of the hypokalemia of Cushing's syndrome, but in the case we are presenting, it is suggested that this drug blocks the action of mitotane. Report of a Case A 65-year-old woman with features of florid Cushing's

In this case of sensitization to erythrocytes, painful purpuric nodules, evanescent neurological complaints, and abdominal pain developed in a patient three weeks after a traumatic ecchymosis. All hematologic and blood clotting studies were normal. Lesions could be reproduced locally by intradermal injections of either autologous whole red blood cells, autologus red blood cell stroma, or purified protein derivative (PPD) of tubercle bacilli, but they could not be reproduced by similar preparations of autologous red blood cell hemolysate, autologus plasma, histamine, calf-thymus deoxyribonucleic acid, salmon-sperm DNA, phosphatidyl-I-serine, or old tuberculin. The patient had an excellent response to cyproheptadine hydrochloride but later was free of lesions after spontaneously stopping treatment.