Comparison of external calibration and isotope dilution LC-ICP-MS/MS for quantitation of oxytocin and its selenium analogue in human plasma.

In the present study, a method for quantitation of the pharmaceutical peptide oxytocin (OT) and its diselenide-containing analogue (SeOT) in human plasma was developed using gradient elution LC-ICP-MS/MS. Plasma samples were precipitated with acetonitrile containing 1.0% TFA in a volume ratio of 1+3 (sample+precipitation agent) before analysis. Post-column isotope dilution analysis (IDA) was applied for quantitation and was compared with external calibration. Both calibration methods appeared to be fit for purpose regarding figures of merit including linearity, precision, LOD, LOQ and recovery. Analysis of OT and SeOT showed that selenium-based analysis is considerably more sensitive and selective compared to the sulfur-based analysis. Despite the relatively simpler setup of external calibration, IDA can be advantageous because it compensates for instrument drift and changes in organic solvent concentration. The method was applied for a stability study showing the degradation of OT and SeOT in plasma. The degradation of SeOT was faster than the degradation of OT in plasma. Thus, possible stability effects should be considered before replacing a disulfide bridge with a diselenide bridge or introducing a diselenide label in a potential drug.

Intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism.

Autism spectrum disorder (ASD) is characterized by core social deficits. Prognosis is poor, in part, because existing medications target only associated ASD features. Emerging evidence suggests that the neuropeptide oxytocin (OXT) may be a blood-based biomarker of social functioning and a possible treatment for ASD. However, prior OXT treatment trials have produced equivocal results, perhaps because of variability in patients' underlying neuropeptide biology, but this hypothesis has not been tested. Using a double-blind, randomized, placebo-controlled, parallel design, we tested the efficacy and tolerability of 4-wk intranasal OXT treatment (24 International Units, twice daily) in 32 children with ASD, aged 6-12 y. When pretreatment neuropeptide measures were included in the statistical model, OXT compared with placebo treatment significantly enhanced social abilities in children with ASD [as measured by the trial's primary outcome measure, the Social Responsiveness Scale (SRS)]. Importantly, pretreatment blood OXT concentrations also predicted treatment response, such that individuals with the lowest pretreatment OXT concentrations showed the greatest social improvement. OXT was well tolerated, and its effects were specific to social functioning, with no observed decrease in repetitive behaviors or anxiety. Finally, as with many trials, some placebo-treated participants showed improvement on the SRS. This enhanced social functioning was mirrored by a posttreatment increase in their blood OXT concentrations, suggesting that increased endogenous OXT secretion may underlie this improvement. These findings indicate that OXT treatment enhances social abilities in children with ASD and that individuals with pretreatment OXT signaling deficits may stand to benefit the most from OXT treatment.

The effects of intrapartum synthetic oxytocin on maternal postpartum mood: findings from a prospective observational study.

Postpartum depression (PPD) affects up to 19% of all mothers, with detrimental effects on both mother and child. The antidepressant and anxiolytic effects of plasma oxytocin are well-documented, but it is still disputable whether synthetic oxytocin (synOT) may protect women against postpartum mood alterations. The current study examined the association between synOT intrapartum and maternal mood postpartum using a prospective design. Two hundred sixty women were screened for depressive symptoms in the last trimester of pregnancy and then again 6 weeks and 9 months postpartum using the Edinburgh Postnatal Depression Scale. They also completed Maternity Blues Questionnaire in the first postpartum week. The data concerning the intrapartum interventions and health status of the newborn were extracted from the medical records. Cox proportional hazards regression adjusted for a history of depression, mode of delivery, and childbirth experience showed that synOT predicted a significantly lower risk of PPD (HR = 0.65, 95% CI 0.45-0.95, p = 0.025). The risk factors for PPD included a history of depression (HR = 3.20, 95% CI 2.33-4.40, p < 0.001) and negative childbirth experience (HR = 1.39, 95% CI 1.01-1.90, p = 0.040). Logistic regression adjusted for the same covariates found no significant effect of synOT on maternity blues (OR = 0.64, 95% CI 0.31-1.32, p = 0.23). While synOT administered intrapartum does not affect maternal mood immediately, it may come to effect some weeks after childbirth to protect mothers from developing PPD symptoms.

Role of topical oxytocin in improving vaginal atrophy in postmenopausal women: a randomized, controlled trial.

OBJECTIVE AND DESIGN: Prospective randomized controlled trial to test the effectiveness of topical oxytocin gel to improve vaginal atrophy in postmenopausal women. PATIENTS AND METHODS: A total of 140 postmenopausal women presenting with vaginal atrophy and who satisfied the inclusion and exclusion criteria were randomized into two groups each of 70 patients; they received intravaginal oxytocin gel or placebo gel for 30 days. Serum estrogen level, visual, colposcopic and histological vaginal examination were performed before and after treatment. RESULTS: Forty-seven out of 70 women in the oxytocin gel group improved after treatment and none in the placebo group (p = 0.001). Forty-five participants in the oxytocin group and seven in the placebo group reported relief of dyspareunia (p = 0.001). Thirty-four participants in the oxytocin group and seven in the placebo group reported relief of soreness (p = 0.001). There was no significant difference between the circulating levels of estradiol in both groups before and after treatment (p = 0.4 and 0.6 for the oxytocin group and the placebo group, respectively). CONCLUSION: Oxytocin gel is useful in the restoration of the vaginal epithelium in cases of postmenopausal atrophic vaginitis. Further studies with a longer follow-up period are required to test the long-term effects of oxytocin as a treatment for vaginal atrophy.

Sex differences in stress reactivity after intranasal oxytocin in recreational cannabis users.

Cannabis is the most widely used illicit drugs and the changing legal, political and cultural climate will likely increase cannabis use further. One factor that may underlie the transition from recreational use to problematic use is stress. The hormone oxytocin (OXT) modulates stress and may have therapeutic efficacy for substance use disorders, but few studies have examined OXT in cannabis users. Another factor is sex; although more men smoke cannabis, the transition from recreational to problematic use is faster in women. Using a within-subjects design, the effects of intranasal (i.n.) oxytocin (OXT; 40 IU) administration on stress reactivity (using the Trier Social Stress Test; TSST) and cannabis (5.6% THC) self-administration was assessed in recreational cannabis using men (n = 31) and women (n = 32) relative to i.n. placebo (PBO) and no-stress (NST) conditions. The TSST produced expected subjective and cardiovascular effects compared to the NST. However, in the i.n. OXT-TSST condition, positive subjective effects were lower and negative subjective effects were higher in women compared to PBO administration and compared to men. Further, latency to self-administer cannabis was longer in women than men and women self-administered less cannabis than men regardless of stress condition. There were no differences in cannabis craving as a function of sex, stress, or medication. These results suggest that OXT administration may lead to greater stress reactivity in recreational cannabis users, particularly women, and support growing evidence that sex differences should be carefully considered when examining the therapeutic potential of OXT.

The acute effects of intranasal oxytocin administration on endocrine and sexual function in males.

The role of the neuropeptide oxytocin (OT) ranges from the modulation of neuroendocrine physiological effects to the establishment of complex social and bonding behaviours. Experimental studies in animals, as well as case reports in humans, suggest that OT affects different aspects of sexual behaviour and has predominantly facilitating properties for sexual appetence and performance. Using a previously established experimental paradigm of sexual arousal and masturbation-induced orgasm, this study investigated the acute effects of intranasal OT application (24I.U.) on endocrine parameters and measures of sexual appetence and function in healthy men (n=10). In a double-blind, placebo-controlled, balanced cross-over design, sexual arousal, and orgasm were induced by an erotic film and masturbation. In addition to the continuous recording of endocrine (OT, cortisol, prolactin, epinephrine, norepinephrine) and cardiovascular data (heart rate), parameters of appetitive, consummatory, and refractory sexual behaviour were assessed using the acute sexual experience scale (ASES). OT plasma levels were significantly elevated after intranasal OT throughout the whole experiment (>60 min). In addition, OT treatment induced significantly higher increases in epinephrine plasma levels during sexual activity without affecting cortisol levels, prolactin levels or heart rate. OT treatment did not alter appetitive, consummatory, and refractory sexual behaviour according to the ASES. However, when subjects were asked about their subjective perception of whether OT or placebo had been applied, eight out of 10 subjects in the OT group answered correctly, thus pointing to an altered perception of arousal. In conclusion, intranasally administered OT leads to a marked increase in OT plasma levels together with increased secretion of catecholamines when subjects are engaged in sexual activity in a laboratory setting. As the effects of OT on sexual behaviour were equivocal, future studies should examine possible facilitating effects further by including males, females, and couples in a field setting, taking into account that OT exerts the most prominent behavioural effects in pair bond formations.

Heat-stable sublingual oxytocin tablets as a potential needle-free approach for preventing postpartum hemorrhage in low-resource settings.

Postpartum hemorrhage is a major cause of mortality and morbidity related to childbirth in developing countries. The recommended treatment includes administration of oxytocin; however, oxytocin is a heat-labile protein, and it must be given as an intramuscular injection by skilled health care providers. To address these challenges, we developed a freeze-dried oxytocin fast-dissolving tablet (FDT) for sublingual (SL) needle-free administration. Using methods developed previously, we produced a robust FDT that maintained oxytocin stability at 40 °C, 75% relative humidity for 12 months. This formulation contains 9% sucrose, 1.5% (hydroxypropyl)methyl cellulose, 9% mannitol, 4% dextran, 1% carbomer, 1% sodium taurocholate, and 100 IU oxytocin. An in vitro study showed a > 30% reduction in tissue transepithelial electrical resistance after treatment with the oxytocin FDT, implying an increase in the permeability of the mucosal tissue to oxytocin. Anesthetized Yucatan miniature swine were administered a SL FDT, and blood was periodically collected for a pharmacokinetic study. Higher plasma concentrations were seen when larger SL doses were given. The maximum concentrations for SL and intramuscular doses in anesthetized pigs were 207 and 612 pg/mL, respectively. Whether the levels attained will be sufficient to elicit beneficial results in humans is yet to be determined. This study demonstrates the feasibility of our approach for developing a heat-stable oxytocin tablet that can be administered successfully via the SL route.

Oxytocin decreases corticosterone and nociception and increases motor activity in OVX rats.

OBJECTIVES: In the present study the effects of oxytocin administered subcutaneously (s.c.) or intravaginally (i.vag.) on spontaneous motor activity, nociceptive thresholds and plasma corticosterone levels were examined in female ovariectomized (OVX) rats. METHODS: Oxytocin (1 mg/kg s.c. or 100 microg i.vag.) was administered once a day for 10 days to OVX rats. Controls received saline s.c. or cellulose gel i.vag. Spontaneous motor activity was observed in an open-field arena, nociceptive thresholds were investigated by the tail-flick test, and corticosterone and oxytocin plasma levels were measured by radioimmunassay, 3, 4 and 5 days respectively, after the end of the treatment period. RESULTS: Both oxytocin administered s.c. and i.vag. increased forward locomotion (p<0.05) and nociceptive thresholds (p<0.05) significantly. In addition, oxytocin s.c. increased the amount of locomotor activity (p<0.05). Plasma corticosterone levels were decreased (p<0.05) and oxytocin levels were unchanged when measured 5 days after the last administration of oxytocin s.c. or i.vag. CONCLUSION: The present data indicate that oxytocin induces a spectrum of long-lasting effects in OVX rats, including an increase in spontaneous motor activity, elevation of nociceptive thresholds and decrease of corticosterone levels. Similar effects may be induced by estrogens. In addition, these data indicate that i.vag. administration of oxytocin may be used to induce oxytocin-mediated effects.

Evaluating misoprostol content in pregnant women with hourly oral administration during labor induction by microElution solid phase extraction combined with liquid chromatography tandem mass spectrometry.

Misoprostol is a widely used alternative of prostaglandin for labor induction. Based on previous studies, we envision that small and frequent oral dosage of misoprostol is an effective method for labor induction. To monitor the misoprostol content during labor induction, a rapid, sensitive, and selective microElution solid phase extraction (µElution SPE) combined with liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed. Using µElution SPE could minimize the sample consumption and elution volume in order to maximize the sample enrichment and throughput. The misoprostol acid, a metabolite of misoprostol, was gradient separated in a Bidentate C18 column, then quantified by highly-selective reaction monitoring (H-SRM) in a total run time of 6min. The developed method was optimized and validated in human plasma, and showed linear range of 0.01-10ng/mL. The limit of detection (LOD) was 0.001ng/mL. The recovery ranged from 89.0 to 96.0%, and no significant matrix effect or carryover was observed. The precision, accuracy and stability were met with the criteria of U.S. FDA guidance. The developed method was successfully applied to evaluate misoprostol concentration during labor induction in pregnant women. The concentration-time profiles approves that hourly oral administration of misoprostol is a safe and effective method without drug accumulation for labor induction.

Rebound increase in fetal breathing movements after 24-h prostaglandin E2 infusion in fetal sheep.

We investigated the hypothesis that the precipitous decrease in prostaglandin E2 (PGE2), a potent inhibitor of fetal breathing, from high plasma concentrations during labor causes a rebound stimulation of breathing without newborn concentrations falling below prelabor fetal values. Fetal plasma PGE2 concentration was gradually increased from 384 +/- 82 (SE) pg/ml in 2-h steps [0 (baseline), 1.5, 3, and 6 micrograms/min] to labor levels (1,230 +/- 381 pg/ml at 6 micrograms/min) and then was maintained for 24 h (n = 9). PGE2 at 1.5 micrograms/min significantly decreased breathing incidence [from 42 +/- 4 (baseline) to 14 +/- 4%] and breath amplitude (from 2.1 +/- 0.5 to 1.5 +/- 0.2 arbitrary units) and increased breath-to-breath interval (from 1.16 +/- 0.07 to 1.56 +/- 0.06 s). No further dose-related changes were observed. During the first 2 h after PGE2 infusion was stopped, PGE2 concentration returned to basal (352 +/- 64 pg/ml) but breathing incidence and amplitude were significantly higher (74 +/- 8% and 2.4 +/- 0.3 arbitrary units, respectively) and breath-to-breath interval was significantly lower (0.95 +/- 0.10 s) than were basal levels. Changes arose within approximately 15 min and were maintained for at least 4 h. Breathing did not change significantly in the saline-treated group (n = 7). Results suggest that the rapid decrease in plasma PGE2 concentration at birth promotes the onset of breathing.

Determination of misoprostol free acid in human breast milk and serum by gas chromatography/negative ion chemical ionization tandem mass spectrometry.

To study an expected transition of misoprostol from human blood into breast milk, a novel method for the determination of its active metabolite misoprostol acid (MPA) was developed. MPA was determined in serum and breast milk samples by an isotope dilution assay using gas chromatography/negative ion chemical ionization tandem mass spectrometry (GC/NICI-MS/MS). After addition of (15S)-15-methylprostaglandin E(2) (15-methyl-PGE(2)) as an internal standard, MPA was extracted from both matrices using a reversed-phase cartridge. The prostanoids were derivatized with O-2,3,4,5,6-pentafluorobenzylhydroxylamine hydrochloride (PFBHA) and 2,3,4,5,6-pentafluorobenzyl bromide (PFBB) to the pentafluorobenzyl oxime (PFBO)-pentafluorobenzyl ester (PFB) derivatives. The sample was subjected to thin-layer chromatography with ethyl acetate-hexane (1 : 1 (v/v)) as the developing solvent. The corresponding zone was extracted. After derivatization to the trimethylsilyl ether, MPA was determined by GC/NICI-MS/MS using the [molecule (M) - pentafluorobenzyl (PFB)](-) ([P](-)) ions as precursor in the negative ion chemical ionization mode. The product ions used for quantification were [P - 2TMSOH - C(6)F(5)CH(2)OH](-) (MPA) and [P - 2TMSOH - C(6)F(5)CH(2)OH - CO(2)](-)(15-methyl-PGE(2)), respectively. The limit of quantification for MPA was approximately 1 pg ml(-1) in breast milk and serum samples. The correlation coefficients of the calibration curves for MPA were r > 0.997 in the 0.5-2000 pg ml(-1) range for both tested matrices.

Comparison of the bioavailability and pharmacokinetics of oral methylergometrine in men and women.

OBJECTIVE: To assess and compare the pharmacokinetics and bioavailability of methylergometrine (ME) in men and non-pregnant women. DESIGN: A cross-over design was used for an oral dose of 0.125 mg and an intravenous dose of 0.200 mg of ME in 6 men and 6 non-pregnant women (parallel-design in gender). RESULTS: After intravenous administration, the pharmacokinetic profile of ME was described with a 2-compartment model. The distribution half-life (t1/2 alpha) in men was 0.19 +/- 0.27 h, in women 0.10 +/- 0.04 h, the elimination half-life (t1/2 beta) 1.85 +/- 0.28 h, respectively, 1.94 +/- 0.34 h and the total body clearance (CL) 33.2 +/- 11.8 l.h-1, and, respectively, 22.18 +/- 3.10 l.h-1. For these intrinsic pharmacokinetic parameters differences between men and women were not statistically significant. After oral administration, the pharmacokinetic profile was described with a 1-compartment model. The lag time was subject dependent and was significantly longer in men 0.33 +/- 0.09 h than in women 0.09 +/- 0.07 h. T1/2 beta in men was 2.08 +/- 0.43 h and was longer than in women 1.42 +/- 0.31 h (p = 0.012). In both men and women a large variation of bioavailability was shown ranging between 22% and 138%. CONCLUSION: This study with oral methylergometrine showed a comparable large interindividual variability in bioavailability in both men and women.

The pharmacokinetics of the prostaglandin E1 analogue misoprostol in plasma and colostrum after postpartum oral administration.

OBJECTIVE: To study pharmacokinetics of prostaglandin E1 analogue, misoprostol in plasma and colostrum after postpartum oral administration. STUDY DESIGN: Twenty women received 600 microg doses of misoprostol orally after delivery. Plasma levels of the principal metabolite, misoprostol acid, were measured at 2, 10, 20, 30, 40, 50, 60, 90, 120, 180, 240 and 300 min (48 samples). Colostrum was expressed from the breasts to measure misoprostol acid at 60, 120, 180, 240, and 300 min (24 samples). Assay was done using isotope dilution gas chromatography (GC)/negative ion chemical ionisation mass spectrometry (MS). RESULTS: The plasma concentration of misoprostol acid rose quickly. Two minutes after oral administration its mean level was 91.5 pg/ml, peaked at 20 min (344 pg/ml), then fell steeply by 120 min (27.8 pg/ml) and remained low for the duration of the study. Misoprostol acid in colostrum reached maximum concentration of 20.9 pg/m within 1h after oral administration. It then declined gradually to 17.8 pg/ml at 2h, 2.8 pg/ml at 4h and to <1 pg/ml at 5h. Areas under misoprostol concentration versus time curves up to 5h were 290.1 pgh/ml in the plasma and 51.4 pgh/ml in colostrum, respectively. CONCLUSION: Misoprostol acid is secreted in colostrum within 1h of oral administration of 600 microg of misoprostol; the pharmacokinetics of misoprostol after oral administration during postpartum is similar to that of other pregnancy periods.

Oral misoprostol is rapidly absorbed in postpartum women at term.

OBJECTIVE: To determine the rate of bioavailability of oral misoprostol in the tablet and a new capsule form in women with term pregnancies in the postpartum period. METHODS: Twenty-seven women received 400 microg of misoprostol orally after delivery of the fetal vertex in either the standard tablet form or crushed in methylcellulose capsules prepared in our pharmacy. Serum levels of misoprostol free acid, the principal metabolite, were measured at 5-, 15- and 30-min intervals after administration of the medication. The pharmacokinetics of the tablet and capsule groups were then compared. RESULTS: Twenty patients were included in the analysis. At 5 min, there was a trend towards a statistically significant difference in the concentration of misoprostol acid in the tablet group (89 pg/ml) versus the capsule group (20 pg/ml) (p = 0.007). No significant difference in plasma concentration was noted in the two groups at 15 min (tablet group, 256 pg/ml; capsule group, 245 pg/ml; p = 0.85) or 30 min (tablet group, 381 pg/ml; capsule group, 455 pg/ml; p = 0.45). CONCLUSION: Oral misoprostol is rapidly absorbed and bioavailable in the postpartum period. Misoprostol may prove useful in postpartum management. The novel packaging of misoprostol in capsule form allows for double-blinded studies with similar pharmacokinetics to the standard tablet.

Effect of oxytocin and its long-acting analog on milk let-down and intramammary pressure in healthy lactating sows.

Ten healthy lactating sows were given single IV injections of 5 to 10 IU of oxytocin and single IV or IM injections of 0.2 to 0.6 mg of deamino-1-monocarba-(2-O-methyltyrosine)-oxytocin [d(COMOT)]. Studies were done with d(COMOT) concerning the dose-response relationship, the influence of the lactation stage on the duration of the milk let-down effect, and the difference between the IV and IM injections. The mean duration of response was 14 minutes for oxytocin and 6.2 hours for d(COMOT). Intramammary pressure was also measured in 3 sows, using 10 IU of oxytocin IV or 0.6 mg of d(COMOT) IV. Oxytocin resulted in a strong initial increase of the intramammary pressure for about 7 minutes. The d(COMOT) caused the same initial response, followed by secondary oscillations lasting for at least 4 hours.

[Plasma prostaglandin E2 in pregnant women undergoing labor induction with endocervical gel application]. / Prostaglandina E2 plasmática en mujeres embarazadas sometidas a inducción del trabajo de parto con aplicación endocervical de gel.

The authors describe an assay that quantify with precision the plasmatic prostaglandin E2 (PGE2). The aim of this study was to evaluate the effect of the gel formulation PGE2 endocervical in the induction of labour. We have studied 26 pregnant women without disease at the term of the pregnancy. The blood sample was collected before and 30 minutes after the labor induction in tubes with 10 mg EDTA Na2 and 5 microg of aspirin. The PGE2 was isolated by extraction and chromatography with 70-100% recovery. The concentration was evaluated by a completion assay with RIA. The PGE2 in plasma was found before and after the induction of labor with the following results: 347 +/- 51.6 and 719 +/- 128 pg/ml. The data was compared by the Student's t test for paired values (df = 50, t = 13. 22 and p < 0.0001). We can conclude that in pregnant women the concentration of PGE2 in plasma was double after the labor induction with the sensitivity in 1.25 pg/tube and the reproducibility 4.6% intraassay and 7% interassay showing that the method is sensitive, reproducible and efficient for the PGE2.

CSF and blood oxytocin concentration changes following intranasal delivery in macaque.

Oxytocin (OT) in the central nervous system (CNS) influences social cognition and behavior, making it a candidate for treating clinical disorders such as schizophrenia and autism. Intranasal administration has been proposed as a possible route of delivery to the CNS for molecules like OT. While intranasal administration of OT influences social cognition and behavior, it is not well established whether this is an effective means for delivering OT to CNS targets. We administered OT or its vehicle (saline) to 15 primates (Macaca mulatta), using either intranasal spray or a nebulizer, and measured OT concentration changes in the cerebral spinal fluid (CSF) and in blood. All subjects received both delivery methods and both drug conditions. Baseline samples of blood and CSF were taken immediately before drug administration. Blood was collected every 10 minutes after administration for 40 minutes and CSF was collected once post-delivery, at the 40 minutes time point. We found that intranasal administration of exogenous OT increased concentrations in both CSF and plasma compared to saline. Both delivery methods resulted in similar elevations of OT concentration in CSF, while the changes in plasma OT concentration were greater after nasal spray compared to nebulizer. In conclusion our study provides evidence that both nebulizer and nasal spray OT administration can elevate CSF OT levels.

Social approach and avoidance behaviour for negative emotions is modulated by endogenous oxytocin and paranoia in schizophrenia.

Patients with schizophrenia suffer from dysfunctional social behaviour. Social approach and avoidance (AA) has been associated with motor responses, as the affective valence and gaze direction of facial stimuli can bias push and pull motor tendencies. The aim of this study was to investigate the role of endogenous oxytocin in social AA behaviour in schizophrenia. Basal plasma oxytocin levels were collected from 28 patients who were then given a joystick-based Approach-Avoidance Task (AAT). Reaction times were recorded and AAT effect scores calculated for responses to happy and angry faces, which either had direct or averted gaze. Individual differences in basal oxytocin had a significant relationship with AAT responses, and patients with higher levels of oxytocin tended to avoid angry faces more. Furthermore, greater avoidance of angry faces was correlated with more severe psychotic (positive and general) symptoms and greater paranoia. This suggests that the endogenous effects of oxytocin may be specific to the interpretation of negative threatening emotions in schizophrenia patients, and also provides evidence that psychotic symptoms and paranoia can impact on social AA behaviour by heightening threat avoidance.

Oxytocin reduces reward-driven food intake in humans.

Experiments in animals suggest that the neuropeptide oxytocin acts as an anorexigenic signal in the central nervous control of food intake. In humans, however, research has almost exclusively focused on the involvement of oxytocin in the regulation of social behavior. We investigated the effect of intranasal oxytocin on ingestion and metabolic function in healthy men. Food intake in the fasted state was examined 45 min after neuropeptide administration, followed by the assessment of olfaction and reward-driven snack intake in the absence of hunger. Energy expenditure was registered by indirect calorimetry, and blood was repeatedly sampled to determine concentrations of blood glucose and hormones. Oxytocin markedly reduced snack consumption, restraining, in particular, the intake of chocolate cookies by 25%. Oxytocin, moreover, attenuated basal and postprandial levels of adrenocorticotropic hormone and cortisol and curbed the meal-related rise in plasma glucose. Energy expenditure and hunger-driven food intake as well as olfactory function were not affected. Our results indicate that oxytocin, beyond its role in social bonding, regulates nonhomeostatic, reward-related energy intake, hypothalamic-pituitary-adrenal axis activity, and the glucoregulatory response to food intake in humans. These effects can be assumed to converge with the psychosocial function of oxytocin and imply possible applications in the treatment of metabolic disorders.

Serum oxytocin concentrations in elective caesarean delivery: a randomized comparison of three infusion regimens.

BACKGROUND: The aim of this study was to determine serum oxytocin concentrations following different regimens of prophylactic oxytocin administration in women undergoing elective caesarean delivery. METHODS: Thirty healthy pregnant patients were randomized, after clamping of the umbilical cord, to receive intravenous oxytocin in one of the following groups: G1 (n=9), 10 IU of oxytocin infused over 30 min (0.33 IU/min); G2 (n=11), 10 IU of oxytocin infused over 3 min and 45 s (2.67 IU/min); and G3 (n=10), 80 IU of oxytocin infused over 30 min (2.67 IU/min). Both patient and surgeon were blinded to allocation. Uterine tone was assessed by surgical palpation. Serum oxytocin concentration was determined by enzyme immunoassay before anaesthesia (T0) and at 5 (T5), 30 (T30) and 60 (T60) min after the start of oxytocin infusion. RESULTS: Serum oxytocin concentrations (mean±standard error, ng/mL) were not significantly different in the groups at T0 (0.06±0.02, 0.04±0.02 and 0.07±0.04, respectively, P=0.76), and T60 (0.65±0.26, 0.36±0.26 and 0.69±0.26, respectively, P=0.58). G3 showed higher concentrations than G1 at T5 (3.65±0.74 versus 0.71±0.27, P=0.01) and at T30 (6.19±1.19 versus 1.17±0.37, P<0.01), and were higher than G2 at T30 (6.19±1.19 versus 0.41±0.2, P<0.01). Haemodynamic data and uterine tone were considered satisfactory and similar in all groups. No additional uterotonic agents were needed. CONCLUSION: Serum oxytocin measurements made using enzyme immunoassay in healthy pregnant women undergoing elective caesarean delivery showed that administration of 80 IU oxytocin over 30 min resulted in higher serum oxytocin levels after 5 and 30 min than the two other regimens. The concentrations did not differ between groups at 60 min.