Oxytocin Antagonist Research Articles

High-throughput evolution of near-infrared oxytocin nanosensors enables oxytocin imaging in mice and prairie voles.

Oxytocin is a neuropeptide involved in regulating social and emotional behavior. Current techniques for oxytocin imaging are generally limited in spatial and temporal resolution, real-time imaging capacity, selectivity for oxytocin over vasopressin, and application in young and non-model organisms. To address these issues, we developed a method to evolve purely synthetic molecular recognition for oxytocin on the surface of near-infrared fluorescent single-walled carbon nanotubes (SWCNT) using single-stranded DNA (ssDNA). The best-performing nanosensor nIROT-SELEC reversibly undergoes up to a 172% fluorescence increase in response to oxytocin with micromolar dissociation, nanomolar limit of detection, and and high selectivity over oxytocin analogs, receptor agonists and antagonists, and co-released neurochemicals. We next demonstrated the versatility of nIROT-SELEC by performing live imaging of synaptic evoked oxytocin released in acute brain slices of mice and prairie voles. Our method for high throughput evolution of neuropeptide nanosensors holds promise to enable synaptic scale visualization of neuropeptide signaling in the brain cross different species and developmental stages, to advance the study of neurochemical signaling for its role in both health and disease.

Combination of rTMS and oxytocin agonist attenuate depression-like behavior after postpartum depression in mice.

The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) categorizes postpartum depression (PPD) as a subtype of Major Depressive Disorder (MDD) with peripartum onset, generally arising within the initial trimester following delivery. This acute psychiatric condition is characterized by feelings of worthlessness, insomnia, extreme anxiety, or maternal neglect. Intranasal oxytocin (OT) and transcranial magnetic stimulation (TMS) have the potential to address impaired social cognition; nonetheless, their neuronal underpinnings, along with their safety and efficacy, are little comprehended. This study examines the effects of rTMS stimulation with an oxytocin agonist or antagonist in a PPD model. We employed the maternal separation with early weaning (MSEW) strategy for 21days to attain our objective. Oxytocin acetate (agonist) and atosiban (antagonist) were administered by injection twice daily for three consecutive days following the model according to the established protocol. A single session of rTMS involved the application of high-frequency stimulation (20Hz) one hour following the final injection. Behavioral testing and brain collection were conducted 12h post-rTMS. The results indicated that treatment with OT followed by rTMS stimulation decreased neuronal cell death and microglial activation, meanwhile enhancing synaptic plasticity through the upregulation of PSD95, Synapsin I, and Synaptophysin. Simultaneously, both OT therapy and repetitive transcranial magnetic stimulation demonstrated a significant capacity to alter autophagy activity and astrocyte function. Nonetheless, OTA therapy followed by rTMS did not exhibit the same pattern of outcomes. Our findings indicate that the combination of rTMS stimulation and an oxytocin agonist in a PPD model may mitigate depression-like behavior.

O-029 Atosiban in women with previous single implantation failure undergoing frozen-thawed blastocyst transfer: a placebo-controlled randomized trial

Abstract Study question Does the administration of Atosiban before frozen-thawed blastocyst transfer improve the live birth rate in women with a history of a single implantation failure? Summary answer In women with a single implantation failure undergoing frozen-thawed blastocyst transfer, Atosiban did not improve the ongoing pregnancy rate. What is known already Uterine peristalsis preceding embryo transfer is believed to adversely impact the success rates of IVF. Atosiban can reduce uterine peristalsis and act as a role of oxytocin antagonist. The effectiveness of Atosiban in the general population of IVF patients has not been conclusively shown by randomised clinical trials or meta-analyses. It has been suggested that women with previous implantation failure may potentially benefit from the use of Atosiban, particularly in the presence of uterine peristalsis. We aim to evaluate if Atosiban before embryo transfer increases live birth rate in women undergoing frozen-thawed blastocyst transfer? Study design, size, duration We conducted a single-centre, double-blind placebo randomised controlled trial (RCT) in women with previous single implantation failure undergoing frozen-thawed blastocyst transfer. Between July 2019 and June 2023, we randomised 1,100 participants to either Atosiban or placebo. The primary outcome was live birth (≥20 weeks of gestation) in the first FET after randomization. In this abstract, we present results on ongoing pregnancy. Data on live birth will be available at the conference. Participants/materials, setting, methods We randomised women with a history of one failed fresh or frozen blastocyst, with at least one cryopreserved blastocyst into two groups on the day of transfer. In the Atosiban group, women were administered 37.5mg of Atosiban intravenously 30-min prior to FET. In the placebo group, women received a saline infusion for the same duration. Uterine peristalsis was measured using transvaginal ultrasound prior to administration of study drugs. The analysis was done based on intention-to-treat. Main results and the role of chance The ongoing pregnancy rates were 50.46% (277/549) and 46.82% (258/551) in the Atosiban and control groups, respectively (RR 1.08, 95% CI 0.95 to 1.22, P = .23). Uterine peristalsis was measured in 720 (65%) of all participants. Within this cohort, of the 163 (22%) women with abnormal contractions, the ongoing pregnancy rates were 51.9% and 41.7%, respectively (RR 1.25, 95% CI 0.90 to 1.73, P = .19). Among 208 women (29%) with peristalsis but without abnormal contraction waves, ongoing pregnancy rates were 50.9% and 48.0% (RR 1.06, 95% CI 0.81 to 1.40, P = .67). In 349 women (48%) without peristalsis, the ongoing pregnancy rates were 48.6% in the Atosiban group versus 50.6% in the control group (RR 0.96, 95% CI 0.78 to 1.19, P = .71). Limitations, reasons for caution Our study only included women with previous blastocyst implantation failure. Uterine peristalsis was not initially assessed, resulting in only 65% (720/1,100) of the participants having peristalsis measured. In this abstract, we only report on the ongoing pregnancy rate. We will present data on live birth at the congress. Wider implications of the findings In unselected women undergoing frozen-thawed blastocyst transfer with previous single implantation failure, Atosiban does not enhance the ongoing pregnancy rate. Future research regarding Atosiban in IVF should assess uterine peristalsis and focus on women with abnormal contractions. Trial registration number ChiCTR1900022333

The oxytocin antagonist cligosiban reduces human prostate contractility: Implications for the treatment of benign prostatic hyperplasia.

With increasing life expectancy, benign prostatic hyperplasia (BPH) consequently affects more ageing men, illustrating the urgent need for advancements in BPH therapy. One emerging possibility may be the use of oxytocin antagonists to relax smooth muscle cells in the prostate, similar to the currently used (although often associated with side effects) α1-adrenoceptor blockers. For the first time we used live-imaging, combined with a novel image analysis method, to investigate the multidirectional contractions of the human prostate and determine their changes in response to oxytocin and the oxytocin antagonists atosiban and cligosiban. Human prostate samples were obtained and compared from patients undergoing prostatectomy due to prostate cancer as well as from patients with transurethral resection of prostate tissue due to severe BPH. The two cohorts of tissue samples showed spontaneous multidirectional contractions, which significantly increased after the addition of oxytocin. Different to atosiban, which showed ambiguous effects of short duration, only long-acting cligosiban reliably prevented, as well as counteracted, any contractile oxytocin effect. Furthermore, cligosiban visibly reduced not only oxytocin-induced contractions, but also showed intrinsic activity to relax prostatic tissue. Thus, the oxytocin antagonist cligosiban could be an interesting candidate in the search for novel BPH treatment options.

Comparison of Intratympanic Oxytocin and Dexamethasone in Cisplatin Ototoxicity: An Experimental Study.

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 72h 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.

Age-Dependent Effects of Oxytocin and Oxytocin Receptor Antagonists on Bladder Contractions: Implications for the Treatment of Overactive Bladder Syndrome.

Overactive bladder (OAB) is an age-related disorder characterised by unstable bladder contractions resulting in disruptive lower urinary tract symptoms (LUTS), thus creating a profound impact on an individual's quality of life. The development of LUTS may be linked to the overexpression of oxytocin receptors (OXTRs) within the bladder detrusor muscle, resulting in increased baseline myogenic tone. Thus, it is hypothesised that targeting OXTRs within the bladder using oxytocin antagonists may attenuate myogenic tone within the bladder, thereby providing a new therapeutic avenue for treating OAB. Organ bath contractility and immunohistochemistry techniques were conducted on bladder tissue sourced from young rats (7-8 weeks and 10-12 weeks) and older rats (4-5 months and 7-9 months). Organ bath studies revealed that oxytocin (OT) significantly increased bladder contractions, which were significantly attenuated by [β-Mercapto-β,β-cyclopentamethylenepropionyl1, O-Me-Tyr2, Orn8]-Oxytocin) (1 µM) (**** p < 0.0001) and atosiban (10 µM) in both young and older rats (** p < 0.01); in contrast, cligosiban (1 µM and 10 µM) did not inhibit OT-induced contractions in both young and older rats (p ≥ 0.05). Interestingly, cligosiban (1 µM and 10 µM) significantly reduced the frequency of spontaneous contractions within the bladder of both young (*** p < 0.001) and older rats (**** p < 0.0001), while atosiban (10 µM) only demonstrated this effect in older rats (** p < 0.01). Furthermore, immunohistochemistry (IHC) analysis revealed significant colocalization of nuclear-specific oxytocin receptors (OXTRs) in the contractile (smooth muscle) cells within young (** p < 0.01) and older rats (* p < 0.05), indicating OT may be a key modulator of bladder contractility.

Sex-dependent regulation of social avoidance by oxytocin signaling in the ventral tegmental area

It has been hypothesized that oxytocin increases the salience of social stimuli, whether the valence is positive or negative, through its interactions with the ventral tegmental area (VTA). Indeed, oxytocin neurons project to the VTA and activate dopamine neurons that are necessary for social experiences with positive valence. Surprisingly, though, there has not been an investigation of the role of oxytocin in the VTA in mediating social experiences with negative valence (e.g., social stress). Given that there are sex differences in how oxytocin regulates the salience of positively-valenced social interactions, we hypothesized that oxytocin acting in the VTA also alters the salience of social stress in a sex-dependent manner. To test this, female and male Syrian hamsters were site-specifically infused with either saline, oxytocin (9 μM), or oxytocin receptor antagonist (90 μM) into the VTA. Subjects were then exposed to either no defeat or a single, 15 min defeat by one RA. The day following social defeat, subjects underwent a 5 min social avoidance test. There was an interaction between sex and drug treatment, such that the oxytocin antagonist increased social avoidance compared to saline treatment in socially stressed females, while oxytocin decreased social avoidance compared to saline treatment in socially stressed males. Contrary to expectations, these results suggest that oxytocin signaling generally acts to decrease social avoidance, regardless of sex. These sex differences in the efficacy of oxytocin and oxytocin receptor antagonists to alter negatively-valenced social stimuli, however, should be considered when guiding pharmacotherapies for disorders involving social deficits.

Methylation of the Oxytocin, Oxytocin Receptor, and Vasopressin Gene Promoters in Tobacco Use Disorder during Cessation

Introduction: Vasopressin (AVP) and oxytocin (OT) exert sex-specific effects on social pair bonding and stress reactions while also influencing craving in substance use disorders. In this regard, intranasal oxytocin (OT) and AVP antagonists present potential treatments for tobacco use disorder (TUD). Since transcription of both hormones is also regulated by gene methylation, we hypothesized sex-specific changes in methylation levels of the AVP, OT, and OT receptor (OXTR) gene during nicotine withdrawal. Methods: The study population consisted of 49 smokers (29 males, 20 females) and 51 healthy non-smokers (25 males, 26 females). Blood was drawn at day 1, day 7, and day 14 of smoking cessation. Craving was assessed with the questionnaire on smoking urges (QSU). Results: Throughout cessation, mean methylation of the OT promoter gene increased in males and decreased in females. OXTR receptor methylation decreased in females, while in males it was significantly lower at day 7. Regarding the AVP promoter, mean methylation increased in males while there were no changes in females. Using mixed linear modeling, CpG position, time point, sex, and the interaction of time point and sex as well as time point, sex, and QSU had a significant fixed effect on OT and AVP gene methylation. The interaction effect suggests that sex, time point, and QSU are interrelated, meaning that, depending on the sex, methylation could be different at different time points and vice versa. There was no significant effect of QSU on mean OXTR methylation. Discussion: We identified differences at specific CpGs between controls and smokers in OT and AVP and in overall methylation of the AVP gene. Furthermore, we found sex-specific changes in mean methylation levels of the mentioned genes throughout smoking cessation, underlining the relevance of sex in the OT and vasopressin system. This is the first study on epigenetic regulation of the OT promoter in TUD. Our results have implications for research on the utility of the AVP and OT system for treating substance craving. Future studies on both targets need to analyze their effect in the context of sex, social factors, and gene regulation.

Effectiveness of atosiban in women with previous single implantation failure undergoing frozen-thawed blastocyst transfer: study protocol for a randomised controlled trial

BackgroundUterine contractions may interfere with embryo implantation in assisted reproductive technology. To reduce these contractions and improve success rates, the oxytocin antagonist atosiban has been suggested for administration during embryo...

The Present and the Future of Medical Therapies for Adenomyosis: A Narrative Review.

Uterine Adenomyosis is a benign condition characterized by the presence of endometrium-like epithelial and stromal tissue in the myometrium. Several medical treatments have been proposed, but still, no guidelines directing the management of adenomyosis are available. While a hysterectomy is typically regarded as the definitive treatment for adenomyosis, the scarcity of high-quality data leaves patients desiring fertility with limited conservative options. Based on the available data, the levonorgestrel-IUD appears to offer the most favorable outcomes. Other treatments, including GnRH antagonists, dienogest, prolactin, and oxytocin modulators, show promise; however, further data are required to establish their efficacy definitively. Furthermore, there are many emerging therapies that have been developed that seem worthy of consideration in the near future. The aim of this narrative review was to explore the current medical treatments available for adenomyosis and to provide a glimpse of future therapies under assessment. For this scope, we performed a literature search on PubMed and Medline from incept to September 2022 using the keywords: "medical treatment", "non-steroidal anti-inflammatory", "progesterone intrauterine device", "dienogest", "combined oral contraceptives", "gonadotropin releasing hormone agonist", "gonadotropin releasing hormone antagonist", "danazol", "aromatase inhibitors", "ulipristal acetate", "anti-platelet therapy", "dopamine", "oxytocin antagonists", "STAT3", "KRAS", "MAPK", "micro-RNA", "mifepristone", "valproic acid", "levo-tetrahydropalamatine", and "andrographolide". The search was limited to articles in English, with subsequent screening of abstracts. Abstracts were screened to select relevant studies.

Intranasal oxytocin does not change partner preference in female titi monkeys (Plecturocebus cupreus), but intranasal vasopressin decreases it.

Strong social bonds are critical to human health; however, the mechanisms by which social bonds are formed and maintained are still being elucidated. The neurohormones oxytocin (OT) and vasopressin (AVP) are considered likely candidates. Primate females, both human and nonhuman, remain understudied populations. Here, we conducted a pharmacological study coupled with a behavioral partner preference test (PPT) to better understand the mechanistic basis of attachment in adult female titi monkeys (Plecturocebus cupreus). This pair-bonding species shares a conserved form of oxytocin with humans and is an excellent model organism to study the neural basis of social bonding. We performed intranasal administration of three doses of oxytocin (IN-OT), two doses of vasopressin (IN-AVP), one dose of an oxytocin antagonist (IN-OTA) and one dose of a saline treatment. We found that compared to the saline control, the IN-AVP treatment (lower dose, 40 IU/kg) decreased the time spent in proximity to the partner and increased lip-smacking toward the stranger. We found no effects of IN-OT or IN-OTA manipulation on partner preference. In contrast, low-dose IN-AVP weakened the partner preference in female titi monkeys.

Oxytocin receptor antagonism during early vocal learning reduces song preference and imitation in zebra finches

In species with vocal learning, acquiring species-typical vocalizations relies on early social orienting. In songbirds, for example, learning song requires dynamic social interactions with a “tutor” during an early sensitive period. Here, we hypothesized that the attentional and motivational processes that support song learning recruit the oxytocin system, which is well-understood to play a role in social orienting in other species. Juvenile male zebra finches naïve to song were each tutored by two unfamiliar adult males. Before exposure to one tutor, juveniles were injected subcutaneously with oxytocin receptor antagonist (OTA; ornithine vasotocin) and before exposure to the other, saline (control). Treatment with OTA reduced behaviors associated with approach and attention during tutoring sessions. Using a novel operant paradigm to measure preference while balancing exposure to the two tutor songs, we showed that the juveniles preferred to hear the song of the control tutor. Their adult songs more closely resembled the control tutor’s song, and the magnitude of this difference was predicted by early preference for control over OTA song. Overall, oxytocin antagonism during exposure to a tutor seemed to bias juveniles against that tutor and his song. Our results suggest that oxytocin receptors are important for socially-guided vocal learning.

Effects of mesotocin manipulation on the behavior of male and female common waxbills

The oxytocin family of neuropeptides is implicated in the regulation of sociality across vertebrates. Non-mammalian homologs of oxytocin, such as isotocin in fish and mesotocin in amphibians, reptiles and birds, all play crucial roles modulating social and reproductive behavior. In this study, we exogenously manipulated the mesotocinergic system in a highly social bird, the common waxbill Estrild astrild, and tested the effects on affiliative and aggressive behavior by performing tests of competition over food. Birds treated with mesotocin decreased almost all the behaviors we studied (movement, feeding, allopreening), while birds treated with an oxytocin antagonist showed a reduction only in social behaviors (aggressions and allopreening). We also found two sex-specific effects: mesotocin reduced allopreening more in males than females, and the oxytocin antagonist reduced aggressiveness only in females. Our results suggest sex-specific effects in the modulation of affiliative and aggressive behaviors via mesotocinergic pathways.

The role of the oxytocinergic system in the antidepressant-like effect of swimming training in male mice

Increasing evidence shows that higher physical activity such as running and swimming exercises is associated with decreased depression-related symptoms. However, underlying mechanisms are not fully understood. This study aimed to investigate whether oxytocinergic system can mediate the antidepressant effect of swimming exercises in mice. First, male NMRI mice were subjected to swimming training for eight weeks, then animals intraperitoneally received oxytocin antagonist (L-368899) 1 h before behavioral tests. We assessed anhedonia and social behavior and behavioral despair using the sucrose preference test, social interaction test, and tail suspension test. Oxytocin levels in the brain and serum were also measured. The results showed that swimming training decreased anhedonia and behavioral despair, whereas it increased social behavior and oxytocin levels in male mice. On the other hand, a subthreshold dose of oxytocin antagonist treatment in exercised mice prevented the antidepressant effect of swimming exercise via increased anhedonia and behavioral despair and decreased social behavior compared to the swimming training group. However, the blockade of oxytocin receptors did not affect oxytocin levels in exercised mice. Overall, these findings suggest that oxytocinergic system can play a role in mediating the antidepressant-like effect of swimming training in mice.

Ghrelin levels in different brain regions in &lt;i&gt;Danio rerio&lt;/i&gt; exposured to stress

BACKGROUND: Literature data indicated that ghrelin may be a stress neuropeptide in some animals, including Danio rerio.&#x0D; AIM: The aim of the study was to measure the levels of ghrelin in Danio rerio brain (forebrain, midbrain, and hindbrain) after predator exposure (predator stress test) and administration of ghrelin and oxytocin antagonists to assess the role of ghrelin in stress response.&#x0D; MATERIALS AND METHODS: The study used 68 Danio rerio, one predator of Cichlasoma nicaraguensis. Ghrelin levels were measured by enzyme-linked immunosorbent assay. The following pharmacological agents were used: 1) ghrelin antagonist hexapeptide [D-Lys3]-GHRP-6 (Tocris, UK); 2) recombinant peptide analog of ghrelin agrelax with a molecular weight of 3.5 kDa, developed at the IEM (both compounds in equal dosages of 0.333 mg/L); corticoliberin (Tocris) at a dosage of 0.4 mg/L; and oxytocin (Gedeon Richter, Hungary) at a dosage of 3.8 L (0.005 IU/L) per 50 mL of aquarium water (0.019 IU/L).&#x0D; RESULTS: In the control group, ghrelin level was determined only in the hindbrain, and ghrelin levels in the forebrain and midbrain were 4 pg/mg of total protein. Contact with a predator led to a significant increase in ghrelin levels in the forebrain and midbrain, but not in the hindbrain. Thus, in fish forebrain, ghrelin levels increased to 966 12 pg/mg of protein, which is almost a 250-fold increase in the indicator compared with the level in intact animals. In the presence of agrelax, [D-Lys3]-GHRP-6, and oxytocin, ghrelin levels in the forebrain and midbrain of stressed fish decreased approximately equally to 88 3, 97 1, and 115 1 pg/mg protein, respectively.&#x0D; CONCLUSION: Thus, stress exposure (contact with a predator) significantly increases ghrelin levels in the forebrain and midbrain but decreases in the hindbrain. Stress-protective peptides (oxytocin, [D-Lys3]-GHRP-6, and agrelax) decreased ghrelin levels in the forebrain and midbrain, and to a lesser extent, in the hindbrain when exposed to stress.

Oxytocin antagonist does not disrupt rabbit maternal behavior despite binding to brain oxytocin receptors.

We explored a possible role of oxytocin (OXT) for the onset and maintenance of rabbit maternal behavior by: (a) confirming that a selective oxytocin receptor antagonist (OTA) widely used in rodents selectively binds to OXT receptors (OXTR) in the rabbit brain and (b) determining the effect of daily intracerebroventricular (icv) injections of OTA to primiparous and multiparous does from gestation day 29 to lactation day 3. OTA efficiently displaced the high affinity, selective oxytocin receptor (OXTR) radioligand, 125 I-labeled ornithine vasotocin analog (125 I-OVTA), but was much less effective at displacing the selective V1a vasopressin receptor radioligand, 125 I-labeled linear vasopressin, thus showing high affinity and selectivity of OTA for rabbit OXTR as in rodents. Further, ICV OTA injections did not modify nest-building, latency to enter the nest box, time spent nursing or the amount of milk produced, relative to vehicle-injected does. The percentage of mothers suckling the litter was also similar between both groups, regardless of parity. Together, our results do not support a role of OXT for the initiation or maintenance of rabbit maternal behavior. Future studies are warranted to determine if OXT participates in fine-tuning additional aspects of the maternal ethogram, for example, circadian periodicity of nursing and nest defense.

Two oxytocin analogs, N-(p-fluorobenzyl) glycine and N-(3-hydroxypropyl) glycine, induce uterine contractions ex vivo in ways that differ from that of oxytocin.

Contraction of the uterus is critical for parturient processes. Insufficient uterine tone, resulting in atony, can potentiate postpartum hemorrhage; thus, it is a major risk factor and is the main cause of maternity-related deaths worldwide. Oxytocin (OT) is recommended for use in combination with other uterotonics for cases of refractory uterine atony. However, as the effect of OT dose on uterine contraction and control of blood loss during cesarean delivery for labor arrest are highly associated with side effects, small amounts of uterotonics may be used to elicit rapid and superior uterine contraction. We have previously synthesized OT analogs 2 and 5, prolines at the 7th positions of which were replaced with N-(p-fluorobenzyl) glycine [thus, compound 2 is now called fluorobenzyl (FBOT)] or N-(3-hydroxypropyl) glycine [compound 5 is now called hydroxypropyl (HPOT)], which exhibited highly potent binding affinities for human OT receptors in vitro. In this study, we measured the ex vivo effects of FBOT and HPOT on contractions of uteri isolated from human cesarean delivery samples and virgin female mice. We evaluated the potency and efficacy of the analogs on uterine contraction, additivity with OT, and the ability to overcome the effects of atosiban, an OT antagonist. In human samples, the potency rank judged by the calculated EC50 (pM) was as follows: HPOT (189) > FBOT (556) > OT (5,340) > carbetocin (12,090). The calculated Emax was 86% for FBOT and 75% for HPOT (100%). Recovery from atosiban inhibition after HPOT treatment was as potent as that after OT treatment. HPOT showed additivity with OT. FBOT (56 pM) was found to be the strongest agonist in virgin mouse uterus. HPOT and FBOT demonstrated high potency and partial agonist efficacy in the human uterus. These results suggested that HPOT and FBOT are highly uterotonic for the human uterus and performed better than OT, indicating that they may prevent postpartum hemorrhage.

Can oxytocin antagonists improve outcomes for women undergoing assisted reproduction?

Can oxytocin antagonists improve outcomes for women undergoing assisted reproduction?

Current and emerging treatment options for premature ejaculation.

Premature ejaculation (PE) is a prevalent male sexual dysfunction. Current standard treatment regimens include behavioural therapies, topical anaesthetics, dapoxetine and other selective serotonin reuptake inhibitors (SSRIs). Most of the pharmacotherapeutic options target neurotransmitters (such as serotonin and oxytocin) that have a role in the ejaculation mechanism. However, these treatments are mildly effective and only provide a temporary delay in the ejaculation latency time, and PE recurs when the treatment is stopped. Thus, a treatment for PE is urgently needed and research is ongoing to find the ideal PE therapy. The efficacy and safety of topical anaesthetics and SSRIs in delaying ejaculation have been confirmed in many well-designed controlled trials. Both preclinical and clinical studies on new-generation SSRIs are ongoing. Moreover, promising results came from clinical trials in which the efficacy of on-demand PE therapies targeting neurotransmitters other than serotonin, such as α1-adrenoceptor antagonists and oxytocin antagonists, was assessed. Surgical intervention and neuromodulation have been proposed as potential treatment options for PE; however, current PE guidelines do not recommend these treatments owing to safety concerns.

EXTRAVASATION OF OXYTOCIN: AN UNUSUAL LABOR EVENT

The present case report highlights the extravasation of oxytocin which is an extremely rare event even in busiest of labour rooms. A 26-year-old second gravida with history of one abortion, presented at 38 weeks period of gestation with complaints of labor pains and suffered this rare incidence of oxytocin infusion extravasation at minimal therapeutic dose. Oxytocin antagonists like Atosiban may be considered in future cases of drug extravasation with oxytocin unresponsive to conservative measures. Further research is needed for management of extravasation of such rarity to prevent devastating complications of amputation &amp; gangrene that may result in loss of permanent limb function even in minimal doses.