bremelanotide and Sexual-Dysfunctions--Psychological

Female sexual response implies a deep intertwining between psychosocial and neurobiological mediators. Regulation of central melanocortin signaling may enhance sexual desire. In premenopausal women with hypoactive sexual desire disorder (HSDD), melanocortin receptor agonist bremelanotide (Vyleesi) has been hypothesized to trigger excitatory brain pathways.. Hereby we summarize bremelanotide's proposed mechanism of action, pharmacokinetics, efficacy and safety data derived from clinical trials. A literature search of peer-reviewed publications on the current evidence on the pharmacotherapy with bremelanotide was performed using the PubMed database.. Bremelanotide appears to be moderately safe and well-tolerated; the most common adverse reaction is nausea (40%). Although data from clinical trials demonstrated a significant change in validated questionnaires, the overall clinical benefit appears to be modest. However, these results should be interpreted in the light of the dramatic challenges in conducting well-designed clinical trials for female sexual dysfunction, due to the significant placebo effect of pharmacotherapy, and the frequent use of outcome measures that are likely to be highly susceptible to expectation biases, such as long periods of recall of sexual and emotional response.

Topics: alpha-MSH; Female; Humans; Libido; Peptides, Cyclic; Sexual Dysfunctions, Psychological

Hypoactive sexual desire disorder (HSDD) is a common female sexual dysfunction and is estimated to affect approximately 10% of women in the United States. It has been suggested that HSDD is associated with an imbalance of hormone and neurotransmitter levels in the brain, resulting in decreased excitation, increased inhibition, or a combination of both. Evidence suggests neurotransmitters, including dopamine (DA), norepinephrine, and serotonin, as well as hormones such as estradiol and testosterone, contribute to female sexual desire and response. Current treatments for HSDD include psychotherapy, and two US Food and Drug Administration-approved medications for premenopausal women: flibanserin, a serotonin mixed agonist and antagonist, and bremelanotide, a melanocortin receptor (MCR) agonist. Melanocortins are endogenous neuropeptides associated with the excitatory pathway of the female sexual response system. MCRs are found throughout the body, including the brain. Bremelanotide is an MCR agonist that nonselectively activates several of the receptor subtypes, of which subtype 4 (MC4R) is the most relevant at therapeutic doses. MC4R is predominantly expressed in the medial preoptic area (mPOA) of the hypothalamus in the brain, and is important for female sexual function. Animal studies suggest that bremelanotide may affect female sexual desire by activating presynaptic MC4Rs on neurons in the mPOA of the hypothalamus, leading to increased release of DA, an excitatory neurotransmitter that increases sexual desire. This review presents what is known about the mechanism of action of bremelanotide in the context of treating HSDD.

Topics: alpha-MSH; Animals; Dopamine; Female; Humans; Neurotransmitter Agents; Peptides, Cyclic; Serotonin; Sexual Dysfunctions, Psychological

Topics: alpha-MSH; Clinical Trials as Topic; Drug Interactions; Female; Humans; Injections, Subcutaneous; Libido; Nausea; Peptides, Cyclic; Receptor, Melanocortin, Type 3; Receptor, Melanocortin, Type 4; Sexual Dysfunctions, Psychological; Treatment Outcome

Bremelanotide (Vyleesi™) is a melanocortin receptor agonist recently approved in the USA for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD), as characterized by low sexual desire that causes marked distress or interpersonal difficulty. It is a self-administered, on-demand subcutaneous therapy. Initially developed by Palatin Technologies who sponsored the Phase 3 clinical trials, bremelanotide was subsequently out-licensed to AMAG Pharmaceuticals Inc. for exclusive North American rights to develop and commercialize the drug, including submitting the New Drug Application to the US FDA. Bremelanotide is a synthetic peptide analogue of the neuropeptide hormone alpha melanocyte-stimulating hormone (α-MSH) with high affinity for the melanocortin type 4 receptor (thought to be important for sexual function), giving it the potential to modulate brain pathways involved in sexual response. This article summarizes the milestones in the development of bremelanotide leading to this first regulatory approval.

Topics: alpha-MSH; Brain; Clinical Trials, Phase III as Topic; Humans; Peptides, Cyclic; Sexual Dysfunctions, Psychological

Topics: Adult; alpha-MSH; Drug Costs; Drug Interactions; Female; Humans; Lactation; Peptides, Cyclic; Pregnancy; Randomized Controlled Trials as Topic; Sexual Dysfunctions, Psychological

Regarding hypoactive sexual desire disorder (HSDD) in women, some reviewers judge the effect size small for medications vs placebo, but substantial for cognitive behavior therapy (CBT) or mindfulness meditation training (MMT) vs wait list. However, we lack comparisons of the effect sizes for the active intervention itself, for the control treatment, and for the differential between the two.. For efficacy trials of HSDD in women, compare effect sizes for medications (testosterone/testosterone transdermal system, flibanserin, and bremelanotide) and placebo vs effect sizes for psychotherapy and wait-list control.. We conducted a literature search for mean changes and SD on main measures of sexual desire and associated distress in trials of medications, CBT, or MMT. Effect size was used as it measures the magnitude of the intervention without confounding by sample size.. Cohen d was used to determine effect sizes.. For medications, mean (SD) effect size was 1.0 (0.34); for CBT and MMT, 1.0 (0.36); for placebo, 0.55 (0.16); and for wait list, 0.05 (0.26).. Recommendations of psychotherapy over medication for treatment of HSDD are premature and not supported by data on effect sizes. Active participation in treatment conveys considerable non-specific benefits. Caregivers should attend to biological and psychosocial elements, and patient preference, to optimize response.. Few clinical trials of psychotherapies were substantial in size or utilized adequate control paradigms. Medications and psychotherapies had similar, large effect sizes. Effect size of placebo was moderate. Effect size of wait-list control was very small, about one quarter that of placebo. Thus, a substantial non-specific therapeutic effect is associated with receiving placebo plus active care and evaluation. The difference in effect size between placebo and wait-list controls distorts the value of the subtraction of effect of the control paradigms to estimate intervention effectiveness. Pyke RE, Clayton AH. Effect Size in Efficacy Trials of Women With Decreased Sexual Desire. Sex Med Rev 2018;6:358-366.

Topics: alpha-MSH; Androgens; Benzimidazoles; Biomedical Research; Cognitive Behavioral Therapy; Female; Humans; Libido; Meditation; Mindfulness; Peptides, Cyclic; Placebos; Serotonin 5-HT2 Receptor Antagonists; Sexual Dysfunctions, Psychological; Testosterone

Hypoactive sexual desire disorder (HSDD) affects nearly 1 in 10 women. Thus, it is essential for pharmacists and other health care providers to be comfortable when discussing a patient's sexual health to ensure appropriate triage so that the specific causes of HSDD can be identified and potential recommendations provided. HSDD is defined as the absence or deficiency of sexual interest and/or desire, leading to significant distress and interpersonal difficulties. As health care providers, pharmacists have a critical role in assessing the presence of HSDD and providing education on available treatment options. This article will review the potential causes of HSDD and low sexual desire, the screening tools available, and the significant role of health care professionals in communicating with patients about their sexual health. An overview of the importance of behavioral modifications, the current pharmacologic options being investigated, and the use of complementary and alternative therapies will also be explored. Currently, buproprion is the primary pharmacologic agent that has shown positive results in treating patients with HSDD. The use of testosterone therapy will not be addressed in this article, as this therapy is described in greater detail elsewhere.

Topics: alpha-MSH; Antidepressive Agents, Second-Generation; Benzimidazoles; Bupropion; Complementary Therapies; Female; Health Behavior; Health Communication; Humans; Peptides, Cyclic; Piperazines; Purines; Receptors, Melanocortin; Reproductive Health; Serotonin Antagonists; Sexual Dysfunctions, Psychological; Sildenafil Citrate; Sulfones; Vasodilator Agents

Human sexual response involves a complex sequencing of interrelated mind/body processes. Few treatment options exist that address the complex multilayered etiological determinants of female sexual dysfunction (FSD).. Review and evaluate the clinical application of centrally acting agents for the treatment of FSD, with particular emphasis on recently released data on bremelanotide.. Review of literature on the treatment of FSD.. Approaches to FSD treatment have ranged from psychological counseling through a variety of medical interventions along the physiological pathways of sexual function and dysfunction. Despite a great deal of research, especially into hormonal and vasoactive substances, few therapeutics have broad consistent applicability and have withstood scientific scrutiny. Recent clinical trials have investigated the potential role of agents which act on the central nervous system for the treatment of FSD.. While the recent data supporting the therapeutic use of centrally acting agents as a monotherapy for FSD are cautiously encouraging, there would seem to be tremendous promise for these centrally acting compounds to be integrated with treatment approaches that utilize other pathways in a multilayered, individualized approach to care.

Topics: alpha-MSH; Central Nervous System Agents; Evidence-Based Medicine; Female; Humans; Peptides, Cyclic; Randomized Controlled Trials as Topic; Research Design; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological; Treatment Outcome; Women's Health

Topics: alpha-MSH; Female; Humans; Libido; Patient Outcome Assessment; Peptides, Cyclic; Quality of Life; Sexual Dysfunctions, Psychological

To evaluate the safety and efficacy of bremelanotide for the treatment of premenopausal women with hypoactive sexual desire disorder.. Two identical phase 3, randomized, double-blind, placebo-controlled, multicenter clinical trials (RECONNECT) evaluated the safety and efficacy of bremelanotide 1.75 mg administered subcutaneously as needed in premenopausal women with hypoactive sexual desire disorder. Patients were randomized 1:1 to 24 weeks of treatment with bremelanotide or placebo. Sample size was estimated based on simulations from key endpoints in patients with hypoactive sexual desire disorder from a prior trial. Coprimary efficacy endpoints were change from baseline to end-of-study in the Female Sexual Function Index-desire domain score and Female Sexual Distress Scale-Desire/Arousal/Orgasm item 13.. Study 301 began on January 7, 2015, and concluded on July 26, 2016. Study 302 began on January 28, 2015, and concluded on August 4, 2016. Of the 1,267 women randomized, 1,247 and 1,202 were in the safety and efficacy (modified intent-to-treat) populations, respectively. Most participants were white (85.6%), from U.S. sites (96.6%), and had a mean age of 39 years. From baseline to end-of-study, women taking bremelanotide had statistically significant increases in sexual desire (study 301: 0.30, P<.001; study 302: 0.42, P<.001; integrated studies 0.35, P<.001) and statistically significant reductions in distress related to low sexual desire (study 301: -0.37, P<.001; study 302: -0.29, P=.005; integrated studies -0.33, P<.001) compared with placebo. Patients taking bremelanotide experienced more nausea, flushing, and headache (10% or more in both studies) compared with placebo.. Both studies demonstrated that bremelanotide significantly improved sexual desire and related distress in premenopausal women with hypoactive sexual desire disorder. The safety profile was favorable. Most treatment-emergent adverse events were related to tolerability and the majority were mild or moderate in intensity.. ClinicalTrials.gov, NCT02333071 (study 301) and NCT02338960 (study 302).. Palatin Technologies, Inc., and AMAG Pharmaceuticals, Inc.

Topics: Adult; alpha-MSH; Central Nervous System Agents; Double-Blind Method; Female; Humans; Injections, Subcutaneous; Libido; Peptides, Cyclic; Premenopause; Psychological Distress; Receptor, Melanocortin, Type 3; Receptor, Melanocortin, Type 4; Sexual Dysfunctions, Psychological; Treatment Outcome

Responder analyses are used to determine whether changes that occur during a clinical trial are clinically meaningful; for subjective endpoints such as those based on patient-reported outcomes (PROs), responder analyses are particularly useful.. To identify the minimal clinically important difference (MCID) for selected scores on questionnaires assessing female sexual functioning and to use these differences to analyze the response in a large, controlled, phase 2b, dose-finding study of bremelanotide in premenopausal women with hypoactive sexual desire disorder (HSDD) and mixed HSDD/female sexual arousal disorder (FSAD).. The responder analyses were performed for the change from baseline to end of study for a total of 7 endpoints. Each PRO endpoint was assessed using at least 1 of 4 types of responder analyses: a planned analysis anchored to MCIDs based on expert estimates (historical anchors); post hoc analyses based on self-reported global benefit; receiver operating characteristic (ROC) curves; and cumulative distribution function. The prespecified analysis groups were all female sexual dysfunction (FSD)-based diagnoses (all study participants), those with HSDD alone, and a combined group of those with FSAD alone plus those with mixed HSDD/FSAD. Post hoc analyses were also performed for subjects with mixed HSDD/FSAD with a primary diagnosis of HSDD.. MCIDs based on the ROC curves for changes in Female Sexual Function Index-desire domain, Female Sexual Distress Scale-Desire/Arousal/Orgasm (FSDS-DAO) total score, FSDS-DAO item 13 and 14 scores, and number of satisfying sexual events.. Outcomes matched those based on input from clinical experts. For all 7 endpoints, responder rates at the 1.75 mg dose in the overall modified intention-to-treat population achieved statistical significance compared with placebo (P ≤ .03).. These responder definitions were subsequently used in the bremelanotide phase 3 registration studies (RECONNECT) that evaluated the safety and efficacy of the bremelanotide 1.75 mg subcutaneous dose in premenopausal women with HSDD.. MCIDs for this study were based on changes from a single-blind phase to account for changes due to the placebo effect. These analyses were restricted to a study population composed only of premenopausal women with a clinical diagnosis of HSDD and/or FSAD and were based on data from the same clinical trial.. Bremelanotide was safe and well tolerated and demonstrated significant improvement in efficacy vs placebo in the phase 2b trial. The multiple responder analyses offer a valuable approach for determining clinically important effects of bremelanotide for HSDD and FSAD. Althof S, Derogatis LR, Greenberg S, et al. Responder Analyses from a Phase 2b Dose-Ranging Study of Bremelanotide. J Sex Med 2019;16:1226-1235.

Topics: Adult; alpha-MSH; Double-Blind Method; Female; Humans; Libido; Peptides, Cyclic; Premenopause; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological; Single-Blind Method; Surveys and Questionnaires

Melanocortin receptor agonists that bind to the melanocortin receptor 4 may cause increases in blood pressure (BP). Bremelanotide is an on-demand, subcutaneous melanocortin-receptor agonist that binds to the melanocortin receptor 4 and is being developed for the treatment of female sexual dysfunction.. We studied the effects of bremelanotide administration on ambulatory BP and heart rate (HR), in a randomized, double-blind, placebo-controlled, and parallel-arm trial of three doses of bremelanotide (0.75, 1.25, and 1.75 mg) in 397 premenopausal women with female sexual dysfunction with normotension or controlled hypertension. Pharmacokinetic exposure was assessed in conjunction with ambulatory BP measurements.. Increases in ambulatory SBP relative to placebo of 2.4 and 3.0 mmHg (1.25 mg; P values: 0.029 and 0.076) and 3.1 and 3.2 mmHg (1.75 mg; P values: 0.006 and 0.027), respectively, occurred following two doses, separated by 24 h at the 0 to 4-h postdose interval; peak increases typically lasted less than 15 min. Similar increases in the DBP were observed. Increases in BP were accompanied by reductions in HR during the 0-4-h interval for the 1.75-mg dose (-4.6 to -4.7 bpm; P < 0.001). Twenty-six participants discontinued after randomization due to prespecified increases in BP but the proportions were similar among the four treatment groups.. These data show that ambulatory monitoring was a useful methodology to detect small, transient increases in ambulatory BP accompanied by reductions in HR following bremelanotide. Results of this trial led to appropriate in-clinic BP monitoring during the larger clinical development trials of this agent for female sexual dysfunction.

Topics: Adult; alpha-MSH; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Female; Heart Rate; Humans; Middle Aged; Peptides, Cyclic; Receptor, Melanocortin, Type 4; Sexual Dysfunctions, Psychological; Young Adult

Evaluate efficacy/safety of bremelanotide (BMT), a melanocortin-receptor-4 agonist, to treat female sexual dysfunctions in premenopausal women.. Patients randomized to receive placebo or BMT 0.75, 1.25 or 1.75 mg self-administered subcutaneously, as desired, over 12 weeks. Primary end point was change in satisfying sexual events/month. Secondary end points included total score changes on female sexual function index and female sexual distress scale-desire/arousal/orgasm.. Efficacy data, n = 327. For 1.25/1.75-mg pooled versus placebo, mean changes from baseline to study end were +0.7 versus +0.2 satisfying sexual events/month (p = 0.0180), +3.6 versus +1.9 female sexual function index total score (p = 0.0017), -11.1 versus -6.8 female sexual distress scale-desire/arousal/orgasm total score (p = 0.0014). Adverse events: nausea, flushing, headache.. In premenopausal women with female sexual dysfunctions, self-administered, as desired, subcutaneous BMT was safe, effective, and well tolerated (NCT01382719).

Topics: alpha-MSH; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Libido; Middle Aged; Peptides, Cyclic; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological; Treatment Outcome; Women's Health

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal).\ This article has been retracted at the request of the Editor-in-Chief. Following the retraction of Dr. Safarinejad's work by other journals, The Journal of Sexual Medicine has undertaken an extensive re-review of all papers Dr. Safarinejad published with the journal. Following an intensive re-evaluation and close scrutiny of the manuscripts, our expert reviewers raised multiple concerning questions about the methodology, results, and statistical interpretation as presented in this article. Dr. Safarinejad was contacted to provide his original data and offer explanations to address the concerns expressed by the reviewers. Dr Safarinejad chose not to respond. Consequently, we can no longer verify the results or methods as presented and therefore retract the article.

Topics: Administration, Intranasal; Adult; alpha-MSH; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Libido; Peptides, Cyclic; Receptor, Melanocortin, Type 3; Receptor, Melanocortin, Type 4; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological; Statistics, Nonparametric; Surveys and Questionnaires; Treatment Outcome; Women's Health

Melanocortins affect multiple physiological responses, including sexual behaviors. Bremelanotide is a synthetic peptide melanocortin analog of alpha-melanocyte-stimulating hormone that is an agonist at melanocortin receptors MC3R and MC4R.. To evaluate a single intranasal dose of bremelanotide for potential effects on physiological and subjective measurements of sexual arousal and desire in premenopausal women with sexual arousal disorder.. Change in vaginal pulse amplitude during neutral and erotic videos after treatment with bremelanotide or placebo and subjects' perceptions of physiological and sexual response within 24 hours of treatment with bremelanotide or placebo.. Eighteen premenopausal women with a primary diagnosis of female sexual arousal disorder were randomly assigned to receive a single intranasal dose of 20 mg bremelanotide or matching placebo in a double-blind manner during the first in-clinic treatment session, and the alternate medication during the second in-clinic treatment session. During each session, subjects viewed a 20-minute neutral video followed by a 20-minute sexually explicit video. Vaginal photoplethysmography was used to monitor vaginal vasocongestion and questionnaires were used to evaluate perceptions of sexual response within the following 24-hour period.. More women reported moderate or high sexual desire following bremelanotide treatment vs. placebo (P = 0.0114), and a trend toward more positive responses regarding feelings of genital arousal occurred after bremelanotide compared with placebo (P = 0.0833). Among women who attempted sexual intercourse within 24 hours after treatment, significantly more were satisfied with their level of sexual arousal following bremelanotide, compared with placebo (P = 0.0256). Vaginal vasocongestion did not change significantly while viewing erotic videos following bremelanotide administration compared with placebo.. This preliminary evaluation suggests the potential for bremelanotide to positively affect desire and arousal in women with female sexual arousal disorder and indicates that bremelanotide is a promising candidate for further evaluation in an at-home study.

Topics: Adult; alpha-MSH; Arousal; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Libido; Patient Satisfaction; Peptides, Cyclic; Premenopause; Receptor, Melanocortin, Type 3; Receptor, Melanocortin, Type 4; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological; Statistics, Nonparametric; Surveys and Questionnaires; Treatment Outcome; Women's Health

Bremelanotide (Vyleesi®), a cyclic heptapeptide, was recently approved for the subcutaneous treatment of premenopausal hypoactive sexual desire disorder. To foster the development of alternative routes of administration, we aimed at determining the oral plasma pharmacokinetics of bremelanotide in beagle dogs. Therefore, we established a UHPLC-MS/MS assay with an LLOQ of 10 pg/mL (9.8 pM) using 100 μL of plasma and validated it according to the guidelines of the US Food and Drug Administration and the European Medicines Agency. Bremelanotide was isolated from plasma by protein precipitation and quantification was performed with positive heated ESI MS/MS in the SRM mode. The calibrated concentration range of 10-10,000 pg/mL was linear showing correlation coefficients > 0.99. In the calibrated range, interday and intraday accuracy ranged from 88.9-100.0 % with corresponding precision < 8 %. Accuracy at the LLOQ ranged from 93.6-100.8 % with corresponding precision < 11 %. Because of the validity of a dilution QC that showed accurate quantification of 10-fold diluted plasma samples (accuracy 99.4 %, precision < 6 %), the assay is suitable for bremelanotide quantification in its effective concentration range up to 100,000 pg/mL. The ultra-sensitive assay was applied to the quantification of bremelanotide plasma concentrations after oral administration to beagle dogs, which indicated minimal oral absorption.

Topics: Administration, Oral; alpha-MSH; Animals; Calibration; Chromatography, High Pressure Liquid; Dogs; Limit of Detection; Male; Mass Spectrometry; Peptides, Cyclic; Premenopause; Quality Control; Reproducibility of Results; Sexual Dysfunctions, Psychological; Spectrometry, Mass, Electrospray Ionization

Topics: Adult; alpha-MSH; Female; Humans; Libido; Nausea; Peptides, Cyclic; Premenopause; Sexual Dysfunctions, Psychological

Topics: alpha-MSH; Female; Humans; Peptides, Cyclic; Sexual Behavior; Sexual Dysfunctions, Psychological

To evaluate the long-term safety and efficacy of bremelanotide as treatment for hypoactive sexual desire disorder in premenopausal women.. Women who completed the 24-week double-blind core phase of RECONNECT, composed of two parallel phase 3 trials (301 and 302) examining the safety and efficacy of bremelanotide compared with placebo in premenopausal women with hypoactive sexual desire disorder, could enroll in the 52-week open-label extension, provided they had not experienced serious adverse events during the core phase. Efficacy was assessed using the coprimary endpoints from the core phase, and all adverse events were collected during the open-label extension. All statistical analyses were descriptive.. The study 301 open-label extension began on July 17, 2015, and concluded on July 13, 2017; the study 302 open-label extension began on October 5, 2015, and concluded on June 29, 2017. Of the 856 eligible patients who completed the core phase, 684 elected to participate in the open-label extension, and 272 completed it. The most common treatment-emergent adverse events considered related to study drug were nausea (40.4%), flushing (20.6%), and headache (12.0%), and the only severe treatment-emergent adverse event experienced by more than one participant in both studies was nausea during the open-label extension. The change in Female Sexual Function Index-desire domain score and Female Sexual Distress Scale-Desire/Arousal/Orgasm item 13 from baseline to end of the open-label extension ranged from 1.25 to 1.30 and -1.4 to -1.7, respectively, for patients who received bremelanotide during the core phase, and 0.70-0.77 and -0.9, respectively, for patients who received placebo during the core phase.. During the 52-week open-label extension of RECONNECT, no new safety signals were observed, and premenopausal women treated with bremelanotide exhibited sustained improvements in hypoactive sexual desire disorder symptoms.. ClinicalTrials.gov, NCT02333071 (study 301) and NCT02338960 (study 302).. Palatin Technologies, Inc., and AMAG Pharmaceuticals, Inc.

Topics: Adult; alpha-MSH; Central Nervous System Agents; Female; Humans; Injections, Subcutaneous; Libido; Long Term Adverse Effects; Peptides, Cyclic; Psychological Distress; Receptor, Melanocortin, Type 3; Receptor, Melanocortin, Type 4; Retrospective Studies; Sexual Dysfunctions, Psychological; Time; Treatment Outcome

Topics: alpha-MSH; Animals; Antidepressive Agents; Arousal; Benzimidazoles; Cognitive Behavioral Therapy; Contraceptives, Oral; Dopamine; Drug Approval; Epinephrine; Female; Humans; Hypothyroidism; Libido; Male; Melanocortins; Orgasm; Peptides, Cyclic; Quality of Life; Rats; Selective Serotonin Reuptake Inhibitors; Serotonin Plasma Membrane Transport Proteins; Sex Hormone-Binding Globulin; Sexology; Sexual Behavior; Sexual Dysfunctions, Psychological; Taboo; United States; United States Food and Drug Administration; Vagina; Women's Health

Topics: alpha-MSH; Double-Blind Method; Female; Humans; Peptides, Cyclic; Premenopause; Sexual Dysfunctions, Psychological; Treatment Outcome

Topics: alpha-MSH; Benzimidazoles; Contraceptives, Oral, Hormonal; Female; Humans; Peptides, Cyclic; Receptors, Melanocortin; Reproductive Health; Serotonin 5-HT1 Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Sexual Dysfunctions, Psychological; Testosterone; Women's Health

Disorders of sexual desire affect an estimated 30% of women in North America and Europe, with etiologies based on interpersonal, personal, and physiological factors. There are currently no pharmacological agents approved for use in the treatment of female sexual dysfunction. This is due, in part, to a focus on the effects of experimental drugs on reflexive components of sexual behavior, such as lordosis, in animal models. Here we report that PT-141, a peptide analogue of alpha-melanocyte-stimulating hormone that binds to central melanocortin receptors, selectively stimulates solicitational behaviors in the female rat. This occurs without affecting lordosis, pacing, or other sexual behaviors. PT-141 did not cause generalized motor activation, nor did it affect the perception of sexual reward. A selective pharmacological effect on appetitive sexual behavior in female rats has not been reported previously, and indicates that central melanocortin systems are important in the regulation of female sexual desire. Accordingly, PT-141 may be the first identified pharmacological agent with the capability to treat female sexual desire disorders.

Topics: alpha-MSH; Animals; Dose-Response Relationship, Drug; Female; Peptides, Cyclic; Rats; Rats, Long-Evans; Receptors, Melanocortin; Sexual Behavior, Animal; Sexual Dysfunctions, Psychological