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Although it is widely used, there is still no valid treatment for ototoxicity caused by the antineoplastic drug cisplatin. In this study, we aimed to investigate the efficacy of intratympanic resveratrol and intratympanic dexamethasone treatment in cisplatin-induced ototoxicity. We also compared intratympanic atosiban (oxytocin antagonist) and oxytocin in cisplatin ototoxicity. In this study, 30 rats (60 ears) were used by separating into 5 groups. Cisplatin, oxytocin, dexamethasone, atosiban and 0.9% NaCl were administered intraperitoneally to all groups separately. Auditory Brainstem Response and Distortion Product Otoacoustic Emission tests were performed on all groups before and 72 h after the procedure. Pre-treatment values were higher than post-treatment values in all groups (p < 0.001). There was no significant prolongation of the post-treatment Auditory Brainstem Response I-IV interval in the oxytocin and dexamethasone groups (p > 0.05). There was no significant decrease in the frequencies of 2832 and 4004 after treatment in the oxytocin and dexamethasone group compared to pre-treatment in Distortion Product Otoacoustic Emission. As a result, it has been shown that intratympanic oxytocin may be an option that can be used in the treatment, although it is not as effective as dexamethasone in preventing cisplatin ototoxicity. [ABSTRACT FROM AUTHOR]

The availability of piperidine, which is widely used for deblocking α-amine groups in solid-phase peptide synthesis using Fmoc methodology, is now significantly limited because this reagent is classified as a controlled substance. Therefore, a search for other available reagents capable of removing Fmoc-protection seems relevant. The suitability of three deblocking reagents based on secondary amines (4-methylpiperidine, pyrrolidine, and piperazine) for the solid-phase synthesis of peptides of various structures, i.e., atosiban (an analog of the neurohypophysial hormone oxytocin), metilin [an agonist of the apelin receptor (APJ)], and a fragment of the 11-19 amino-acid segment of the regulatory myosin light chain was comparatively assessed. These reagents were shown to be suitable alternatives to piperidine for the preparation of the physiologically active peptides being studied. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effects of atosiban on clinical outcomes in patients undergoing frozen-thawed embryo transfer. Methods: The clinical data of 1093 infertile patients who underwent frozen-thawed embryo transfer in our center from January 2019 to December 2020 were retrospectively analyzed (control, 418; atosiban, 675). Propensity score matching (PSM) analysis identified 400 matched pairs of patients. The implantation rate, clinical pregnancy rate, live birth rate, biochemical pregnancy rate, abortion rate, multiple pregnancy rate, and ectopic pregnancy rate between the two groups were compared. Results: Before PSM, patients differed by infertility factors, number of transferred embryos, and endometrial preparation protocol (P < 0.05). After PSM, characteristics were similar in corresponding patients of the atosiban and control groups. After propensity score matching, we found that there was no significant difference in the implantation rate, clinical pregnancy rate, live birth rate, biochemical pregnancy rate, abortion rate, multiple pregnancy rate, and ectopic pregnancy rate in atosiban and control group (P > 0.05). Conclusion: Atosiban did not improve the clinical outcomes of infertile patients with frozen-thawed embryo transfer. [ABSTRACT FROM AUTHOR]

This work is devoted to the large-scale solid-phase synthesis (SPS) of Atosiban, Mpa1-D-Tyr(OEt)-Ile-Thr-Asn-Cys6-Pro-Orn-Gly-NH2 cyclic 1,6 disulfide, the only clinically used oxytocin receptor antagonist. The conditions have been selected for the closure of the disulfide bond (S–S) in the Atosiban molecule both in the solution and solid phase with the minimal formation of by-products. A comparative assessment of the formation of the S–S bond was carried out under various conditions. The formation of by-products during the closure of the disulfide bond has been studied both in solution and on the polymer support. The developed technique allows for the synthesis of Atosiban on an enlarged scale (10–20 mmol) involving the cyclization of a protected intermediate with the formation of the S–S bond during solid-phase synthesis with the minimal formation of by-products. [ABSTRACT FROM AUTHOR]

We assessed the effect of atosiban on pregnancy outcomes following in vitro fertilization (IVF) treatment among infertile women requiring different numbers of embryo transfer (ET) cycles (i.e., one, two, and more than two ET cycles). A longitudinal cohort study was conducted by utilizing the data from the Assisted Reproductive Technology Center in a university tertiary hospital during 2007–2017. Patients receiving IVF treatment with at least one ET cycle were included. Pregnancy outcomes following IVF treatment, including biochemical, clinical, and ongoing pregnancies, were investigated. The association between atosiban and IVF pregnancy was assessed using logistic generalized estimating equation models, with adjustment for time-varying clinical characteristics (e.g., maternal age) across multiple ET cycles for an individual. 403 women with 838 ET cycles were included, where 165 patients required one ET cycle, 133 patients required two ET cycles (a total of 266 ET cycles), and 105 patients required more than two ET cycles (a total of 407 ET cycles). Atosiban use was not significantly associated with pregnancy outcomes among all study infertile women undergoing IVF treatment. However, the results for women requiring more than two ET cycles showed significantly increased pregnancy rates associated with atosiban use (i.e., odds ratios [95% confidence interval] of 4.40 [1.52, 12.73] and 2.85 [1.45, 5.60] for clinical and ongoing pregnancies, respectively). This association was not observed for the women requiring only one or two ET cycles. Atosiban is a potential treatment for enhancing IVF pregnancy, especially among infertile women requiring more than two ET cycles. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the effect of atosiban on the outcomes of infertile women undergoing in vitro fertilization (IVF) with difficult embryo transfers (ETs). This randomized double-blind study enrolled 204 infertile women with difficult ETs during IVF treatment between June 2014 and June 2018. According to a computer-generated randomization list, participants were randomized into placebo (n = 102) and atosiban (n = 102) groups. In atosiban group, atosiban with a total dose of 37.5 mg was administered. All of the patients underwent IVF-ET using cryopreserved embryos. The clinical pregnancy rate per cycle and implantation rate per transfer (45.1% and 26.5%) in atosiban group were significantly higher than those of placebo group (15.6% and 9.7%, respectively; P <.05). This study showed that administration of atosiban during ET was extraordinarily effective for patients with difficult transfers. [ABSTRACT FROM AUTHOR]

Objectives: Evidence for the efficacy of atosiban in improving pregnancy outcomes among patients undergoing assisted reproductive technology (ART) remains inconsistent.Methods: The PubMed, EMBASE, and CNKI databases were searched using keywords such as 'atosiban', 'infertility', and 'ART'. Studies that explored the efficacy of atosiban in the field of ART for patients with embryo transfer (ET) were included if they evaluated pregnancy outcomes. Combing using subgroups and sensitivity analysis were conducted, and risk ratios (RRs), and 95% confidence intervals (CIs) were calculated.Results: Six studies were included. Atosiban treatment could improve pregnancy outcomes for all patients undergoing ET, especially for the subgroups of patients with repeated implantation failure (RIF) (implantation rate: RR = 1.806, 95% CI = 1.473-2.215; clinical pregnancy rate: RR = 1.725, 95% CI = 1.394-2.135; live birth rate: RR = 2.141, 95% CI = 1.494-3.068), as shown by the comparison with placebo or no-treatment groups. However, no statistical significance was detected in subgroups of patients undergoing their first or second ET cycle. In addition, no significant differences were observed in positive pregnancy tests, miscarriage rates, multiple pregnancy rates, or ectopic pregnancy rates.Conclusions: Supplementation with atosiban has a positive effect on ART and embryo transfer procedure, especially for women undergoing their third or more ET cycle. [ABSTRACT FROM AUTHOR]

Aim of the present study was to evaluate effects of ligands of oxytocin receptors on gene expression of neurofilament proteins (nestin and microtubule-associated protein 2 (MAP2)) associated with neuronal differentiation and growth factors (brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF)) related to neuronal growth. Fluorescent staining of F-actin was used to observe morphology of cells. Co-treatment with oxytocin and oxytocin receptor antagonist-atosiban-resulted in significant increase of MAP2 gene expression in SK-N-SH cells. There was no effect of oxytocin on gene expression of growth factors BDNF and NGF. Surprisingly, oxytocin with atosiban significantly increased mRNA levels for both BDNF and NGF. Gene expression of vasopressin receptor (V1aR) significantly decreased in response to vasopressin. Atosiban decreased mRNA levels for oxytocin receptor (OXTR) and V1aR. Oxytocin significantly decreased OXTR and nestin mRNA levels and increased mRNA levels for BDNF and NGF in U-87 MG cells. The densest recruitment of F-actin filaments was observed in apical parts of filopodia in SK-N-SH cells incubated in oxytocin presence. Present data demonstrate complex role of ligands of oxytocin receptors in regulation of gene expression of intermediate filaments and thus, oxytocin might be considered as a growth factor in neuronal type of cells. [ABSTRACT FROM AUTHOR]

Purpose: The current study investigated the potential therapeutic efficiency of atosiban, an oxytocin receptor antagonist, in an experimental endometriosis model. Methods: Endometriosis was surgically induced in 35 female rats during estrus. Four weeks after this procedure, relaparotomy was performed. The viability and dimensions of the endometriosis foci were recorded. Rats were then randomly divided into three groups. In the first group ( n = 8), a daily dose of 0.2 ml 0.9 % NaCl was injected intraperitoneally (i.p.) (control cases). In the second and third groups ( n = 8 and n = 8), 0.5 mg/kg/day i.p. atosiban and 1 mg/day i.p. diltiazem were given, respectively. At the end of the treatment, laparotomy was performed, and the dimensions of the endometriosis foci were recorded. The endometrial implants were processed for histological and immunohistochemical studies. The volumes of endometriotic implants were measured, and immunohistochemical analyses were performed, and compared between the groups. Results: After the treatment with atosiban, volumes of endometriotic implants decreased significantly. Proliferating cell nuclear antigen expression levels were significantly reduced in the atosiban and diltiazem groups compared with the control group. Conclusions: In a rat endometriosis model, atosiban, an agent used for the first time for the medical treatment of endometriosis, has shown significant therapeutic efficiency. [ABSTRACT FROM AUTHOR]

In this study we present the synthesis and some pharmacological properties of fourteen new analogues of neurohypophyseal hormones conformationally restricted in the N-terminal part of the molecule. All new peptides were substituted at position 2 with cis-1-amino-4-phenylcyclohexane-1-carboxylic acid ( cis-Apc). Moreover, one of the new analogues: [ cis-Apc, Val]AVP was also prepared in N-acylated forms with various bulky acyl groups. All the peptides were tested for pressor, antidiuretic, and in vitro uterotonic activities. We also determined the binding affinity of the selected compounds to human OT receptor. Our results showed that introduction of cis -Apc in position 2 of either AVP or OT resulted in analogues with high antioxytocin potency. Two of the new compounds, [Mpa, cis-Apc]AVP and [Mpa, cis-Apc,Val]AVP, were exceptionally potent antiuterotonic agents (pA = 8.46 and 8.40, respectively) and exhibited higher affinities for the human OT receptor than Atosiban ( K values 5.4 and 9.1 nM). Moreover, we have demonstrated for the first time that N -terminal acylation of AVP analogue can improve its selectivity. Using this approach, we obtained compound Aba[ cis-Apc,Val]AVP ( XI) which turned out to be a moderately potent and exceptionally selective OT antagonist (pA = 7.26). [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate the cardiac and cerebral oxidative stress in the offspings of pregnant rats treated with oxytocin antagonist atosiban. Methods: Experimentally naive, adult female Wistar-albino rats (200-250 g) were mated with adult male rats for copulation. After confirming pregnancy, eight gravid rats were then randomly assigned into two equal groups. The animals were treated from days 15 to 20 of gestation. One group acted as a control group, and received intraperitoneal (i.p.) injections of saline in a daily dose volume of 6 mg/kg/day. The second group received 6 mg/kg/day i.p. atosiban. On day 21 of gestation, pups were delivered by cesarean. The heart and brain tissues of the newborn rats were dissected and sent for the measurement of total oxidant status, total antioxitant status and oxidative stress index. Results: There was no significant difference in birthweight or in the number of pups between two groups. Newborns from atosiban-treated mothers showed significantly increased oxidative stress in the plasma and heart tissue than that of controls which was confirmed by histological examination ( P < 0.05). Oxidative stress parameters and histopathological results of the brain tissues of newborns were similar between two groups ( P > 0.05). Conclusion: Oxytocin receptor blockage for the treatment of premature delivery may be associated with increased fetal morbidity and mortality secondary to the elevated oxidative stress in the heart of the newborns. [ABSTRACT FROM AUTHOR]

Purpose: Beta-2 adrenoceptor agonistic drugs like ritodrine have been the reference tocolytic drugs, but are associated with cardiovascular side-effects. Atosiban, a newer drug, is a competitive antagonist of oxytocin and has been claimed to have fewer cardiovascular side effects. Until now, there has mainly been a subjective reporting of adverse reactions and few objective cardiovascular data. Evaluation of the acute effects of therapeutic doses of ritodrine and atosiban compared with placebo on cardiac function, large artery properties, blood pressure, and resistance vessels. Methods: A double-blind, randomized trial was carried out in 20 non-pregnant female volunteers. Hemodynamic measurements were made under standardized conditions during kinetic steady state. Cardiac output was measured with echocardiography, large artery properties with an echo-tracking device. The effect on the microcirculation was estimated using the total peripheral resistance index (TPRI). Results: Atosiban did not differ from placebo. With ritodrine, cardiac function increased by 79% compared with placebo because of a rise in heart rate (91%). TPRI decreased by 48%. Ritodrine increased the distensibility of the common carotid artery by 62% and the compliance by 83%, independent of blood pressure. Compliance of the common femoral artery increased independently of pressure by 33% and the distensibility by 59%. Aortic pulse wave velocity was not influenced by either medication. Conclusions: The present study shows potential beneficial vascular effects of ritodrine that are counterbalanced by the cardiac effects. Atosiban has no clinically relevant cardiovascular effects and may be a good alternative for ritodrine in pregnant women at risk of cardiovascular complications. [ABSTRACT FROM AUTHOR]

Background: The importance of tocolysis has been discussed extensively. Beta-2 adrenoceptor agonistic drugs like ritodrine have been the reference tocolytic drugs in most countries. Cardiovascular side-effects are frequent. Atosiban, a newer tocolytic drug, is a competitive antagonist of oxytocin and has fewer cardiovascular side effects. Although large studies exist, there is mainly subjective reporting of adverse reactions with a focus on blood pressure data. Objectives: Evaluation of the acute effects of therapeutic doses of ritodrine and atosiban in comparison to placebo on central and peripheral blood pressures, central-to-peripheral blood pressure amplification and the augmentation index (AIx) in healthy non-pregnant female volunteers. Methods: A double-blind, randomized, crossover trial was carried out in 20 healthy non-pregnant female volunteers. Hemodynamic measurements were performed under standardized conditions. Results: At steady state, central and peripheral pressures did not differ from placebo in the atosiban group. During ritodrine -infusion, central SBP increased by 11% versus placebo (p = 0.012) and peripheral SBP by 10% (p = 0.004). In contrast to atosiban and placebo, blood pressure amplification was absent in the ritodrine group. While the AIx did not change in the atosiban group, with ritodrine, the AIx tended to decrease. Conclusions: The present study shows the significant effects of ritodrine on the cardiovascular system. Atosiban has no significant effects and may be an appropriate alternative to tocolyticum, particularly in cardiovascularly complicated pregnancies. [ABSTRACT FROM AUTHOR]

Carbamazepine (CBZ) is known to produce cognitive side effects being at least partly relevant for driving. In contrast to this, the cognitive effects of oxcarbazepine (OXC) are suspected to be less pronounced. This study aimed to test 900 mg/day OXC as compared to 600 mg/day CBZ with respect to driving. Driving performance of 27 healthy volunteers under subchronic treatment of OXC and CBZ was assessed in a driving simulator with a double-blind, randomized, crossover design including a baseline measurement. The test course contained a representative set of scenarios. Lane-keeping performance, driving mistakes, and eyelid closure (as a behavioral measure of sleepiness) were analyzed. In addition, subjects were asked to assess their driving performance, effort, attention, and sleepiness subjectively. Both drugs had negative effects on driving as reflected in poorer lane-keeping performance, higher rate of driving mistakes, increased sleepiness, and worse subjective ratings. These effects were most obvious in monotonous situations and could be compensated in situations challenging to cognitive and motor driving skills. With respect to all considered parameters, CBZ did more often differ significantly from baseline than OXC. Under both drugs, driving performance was worse than at baseline. Even though deterioration of driving performance was only slightly less pronounced under OXC than under CBZ, it might be recommended as more appropriate than CBZ for epileptic patients who need to drive a car. [ABSTRACT FROM AUTHOR]

The distribution of oxytocin receptors in limbic regions, as well as evidence that exogenous oxytocin modulates affect and fear processing, suggests that this neuropeptide may have a role to play in the treatment of mood disorders. This study compared the effects of acute treatment with the oxytocin receptor agonist, carbetocin with the tricyclic antidepressant, imipramine, using male Sprague–Dawley rats. Intracerebroventricular (i.c.v.; 1, 10, 100 μg/rat), intravenous (i.v.; 2.5, 5 mg/kg), and intraperitoneal (i.p.; 2, 6.4, 20 mg/kg) carbetocin and imipramine (1.8, 5.6, 10 mg/kg, i.p.) were examined in the modified forced swim and open field tests. The mechanism of action of carbetocin was investigated by co-administering it with the oxytocin antagonist, atosiban, either centrally (5 μg/rat, i.c.v.) or systemically (1 mg/kg, i.v.). Imipramine and carbetocin (all three routes of administration) both significantly reduced immobility and increased swimming and/or climbing behavior in the forced swim test. The systemic effects of carbetocin were blocked by central and systemic atosiban co-administration. Only amphetamine (2 mg/kg, i.p.), included as a false positive in order to distinguish whether antidepressant-like effects were due to psychomotor stimulation, increased locomotor activity in the open field test. Carbetocin produced antidepressant-like changes in behavior via activation of oxytocin receptors in the CNS. The similarities between imipramine and carbetocin in the forced swim test suggest that drugs which target the oxytocinergic system may aid both the understanding and pharmacological treatment of depressive illness. [ABSTRACT FROM AUTHOR]

Objective: Atosiban has been shown to be an effective tocolytic agent with a low rate of side effects during 24 to 33 weeks of gestation. Atosiban acts through selective, competitive inhibition of both oxytocin and vasopressin, so that there are reasons to assume that a tocolytic effect can also be achieved earlier in the pregnancy. Study design: In this prospective, randomized pilot study, 20 women in the 18th through 24th week of gestation who presented at our hospital with preterm labor were treated with atosiban. In the control group 20 women received saline infusions. All patients received antibiotic therapy. A cervical cerclage was performed when indicated as was correction of the vaginal pH. Results: The tocolytic effect began after 3- 10 mm (median: 6.5 mm). Treatment time until the complete absence of contractions was 3-12 h (median: 7.5 h). Pregnancies were prolonged between 11.1 and 21.7 weeks (median: 15.6 weeks) in the atosiban group vs. 10.5-19.1 weeks in the control group. If well tolerated, atosiban was continued. There were no significant alterations in the routine laboratory parameters, circulation parameters, and fluid balance. Conclusion: In summary, atosiban showed itself to be effective for tocolytic treatment for premature labor, even during 18 and 24 weeks of pregnancy, while exhibiting its known, favorable profile of side effects. [ABSTRACT FROM AUTHOR]

Prematurity has not decreased significantly over the past 20 years, whereas early prematurity has increased. New tocolytic agents have been developed that are increasingly successful at preventing preterm delivery, and that have improved maternal tolerance. Although their use is not approved of by European or American drug agencies, calcium channel blockers are currently widely used for tocolysis. Their efficacy and the absence of dangerous side effects on mother and fetus justify their use, even as a first line therapy. Oxytocin antagonists are also widely used. Their effectiveness appears to be similar to that of β-adrenergic agonists, but unlike them oxytocin antagonists are devoid of any measurable side effects. They were designed specifically as tocolytics and have been validated by the European Drug Agency. They have a place in the treatment of preterm labor. New molecules are being investigated; they could possibly be used in the future with greater efficacy. [ABSTRACT FROM AUTHOR]

Background:A synthetic oxytocin analogue, barusiban, was shown to potently inhibit oxytocininduced activity of myometrium from term pregnant women. The responsiveness to vasopressin was not influenced by the compound.Objective:To test the effect of barusiban and a reference compound, atosiban, on oxytocin-induced activity of myometrium from women at preterm pregnancy in comparison to myometrium from women at term.Methods:Fifteen preterm (30-36 gestational weeks) and 12 term pregnant women (38-41 weeks) who underwent cesarean delivery donated myometrial tissue for the study. Concentration-response curves following oxytocin administration to isolated myometrial stips were recorded in control experiments, in the presence of barusiban at concentrations of 2.5, 25, and 250 nM, and of atosiban at concentrations of 25, 250, and 750 nM. Effective concentration 50% (EC50) and pA2 values were calculated.Results:Both antagonists in higher concentrations increased the EC50 values to oxytocin. The median pA2 value for preterm myometrium with barusiban was 9.76 and with atosiban 7.86. For term myometrium the corresponding pA2 results were 9.89 and 7.81, respectively. None of these pA2 values differed to any statistically significant degree.Conclusion:The selective oxytocin antagonist, barusiban, concentration-dependently inhibits oxytocin-induced myometrial contractions of both preterm and term myometrium at least as potently as atosiban. It remains to be determined if the selectivity of barusiban for the oxytocin receptor confers an advantage over atosiban as a tocolytic in preterm labor. [ABSTRACT FROM PUBLISHER]

The effects of oxytocin (OT) on gastric emptying, gastrointestinal transit, and plasma levels of cholecystokinin (CCK) were studied in female rats. Gastrointestinal motility was assessed in rats 15 min after intragastric instillation of a test meal containing charcoal and Na251CrO4. Gastric emptying was determined by measuring the amount of radiolabeled chromium contained in the small intestine as a percentage of the initial amount received. Gastrointestinal transit was evaluated by calculating the geometric center of distribution of the radiolabeled marker. Blood samples were collected for CCK radioimmunoassay. After administration of OT (0.2–0.8 mg/kg), gastric emptying and gastrointestinal transit were inhibited, whereas the plasma concentration of CCK was increased in a dose-dependent manner. Atosiban, an oxytocin receptor antagonist, effectively attenuated the OT- induced inhibition of gastric emptying and gastrointestinal transit. However, administration of atosiban alone had no effect on gastric emptying and gastrointestinal transit. The selective CCK1 receptor antagonists, devazepide and lorglumide, effectively attenuated the OT-induced inhibition of gastric emptying and gastrointestinal transit. L-365, 260, a selective CCK2 receptor antagonist, did not alter the OT-induced inhibition of gastric emptying and gastrointestinal transit. These results suggest that OT inhibits gastric emptying and gastrointestinal transit in female rats via a mechanism involving CCK stimulation and CCK1 receptor activation. [ABSTRACT FROM AUTHOR]

The effects of oxytocin (OT) on gastric emptying and plasma levels of cholecystokinin (CCK) were studied in male rats. Gastrointestinal motility was assessed in rats 15 min after intragastric instillation of a test meal containing charcoal and Na251CrO4. Gastric emptying was determined by measuring the amount of radiolabeled chromium contained in the small intestine as a percentage of the initial amount received. Blood samples were collected for OT and CCK radioimmunoassay. After administration of OT (0.2–0.8 mg kg–1), gastric emptying was inhibited, whereas plasma concentrations of OT and CCK were increased in a dose-dependent manner. Atosiban, an oxytocin receptor antagonist, effectively attenuated the OT-induced inhibition of gastric emptying. However, administration of atosiban alone had no effect on gastric emptying. Devazepide (3 mg kg–1), a selective CCKA receptor antagonist, effectively attenuated the OT-induced inhibition of gastric emptying. L-365, 260, a selective CCKB receptor antagonist, did not alter the OT-induced inhibition of gastric emptying. These results suggest that OT inhibits gastric emptying in male rats via a mechanism involving CCK stimulation and CCKA receptor activation. [ABSTRACT FROM AUTHOR]

Objective:Continuous infusion of the selective prostaglandin synthase type-2 inhibitor nimesulide, together with the oxytocin receptor antagonist atosiban, inhibits glucocorticoid induction of labor in sheep. We evaluated the effectiveness of this treatment commencing after the onset of premature labor when prostaglandin concentrations are already significantly elevated.Methods:Premature labor was induced in chronically cannulated fetuses by constant fetal dexamethasone infusion. After the onset of active labor in each ewe, defined as uterine electromyographic (EMG) activity twice basal levels, ewes received combined nimesulide and atosiban (20.0 and 4.12 mg/kg per day, respectively; n = 6) or vehicle (n-methyl-2-pyrrolidone and saline each 1 mL/hour; n = 4) infusions for 48 hours. Maternal and fetal plasma PGFM (13, 14-dihydro-15-keto PGF2α, the stable metabolite of prostaglandin (PG) F2α) and PGE2 concentrations were measured before, during, and after infusions.Results:Four nimesulide- and atosiban-treated ewes successfully completed the 48-hour infusion period with no deliveries occurring during inhibitor treatment, or up to 6 hours after inhibitor treatment. Delivery was delayed in two other ewes, compared with control animals. Uterine EMG activity in nimesulide- and atosiban-treated ewes (n = 4) was significantly reduced during the 48-hour inhibitor treatmenmt period. Maternal and fetal prostaglandin concentrations were significantly decreased in inhibitor-treated ewes during and after the infusions.Conclusions:The combination of nimesulide and atosiban treatment for 48 hours successfully inhibited the progression of active premature labor to delivery. This study further supports the potential value of this treatment regime for the inhibition of premature labor. [ABSTRACT FROM PUBLISHER]