Research Applications
Hypoactive Sexual Desire Disorder (Approved)
PT-141 (Vyleesi) is FDA-approved for HSDD in premenopausal women. Phase 3 RECONNECT trials demonstrated significant improvement in sexual desire scores and reduction in distress related to low sexual desire. Approximately 25% of women achieved clinically meaningful responses.
Male Erectile Dysfunction
Clinical trials in men with erectile dysfunction demonstrated PT-141 efficacy, including in men who failed PDE5 inhibitor therapy. Its central mechanism addresses desire-related ED that vascular agents cannot treat. Studies show improved erections and sexual satisfaction.
Female Sexual Arousal Disorder
Research beyond HSDD explores PT-141 for broader female sexual dysfunction, including arousal and orgasm difficulties, where central neural activation may provide benefit.
Hemorrhagic Shock (Unexpected Application)
Preclinical and early clinical research revealed that MC3R/MC4R activation by PT-141 has potent cardiovascular protective effects in hemorrhagic shock, improving survival and organ perfusion through central sympathetic activation and anti-inflammatory mechanisms.
Depression-Related Anhedonia
The dopaminergic and melanocortin reward pathway activation by PT-141 is being investigated for anhedonia (inability to experience pleasure) in depression, where melanocortin signaling dysfunction may contribute to motivational deficits.
Mechanism of Action
MC3R/MC4R Activation in the CNS
PT-141 activates melanocortin-3 and melanocortin-4 receptors in hypothalamic and limbic brain regions involved in sexual arousal and desire. MC4R activation in the paraventricular nucleus and medial preoptic area stimulates descending pathways that enhance genital arousal responses and modulate dopaminergic circuits involved in sexual motivation.
Dopaminergic Enhancement
MC4R signaling in the hypothalamus potentiates dopamine release in the mesolimbic reward pathway (nucleus accumbens, ventral tegmental area). This enhanced dopaminergic tone increases sexual motivation, desire, and the hedonic aspects of sexual experience.
Oxytocin Pathway Activation
MC4R activation in the paraventricular nucleus triggers oxytocin release, which contributes to genital arousal responses in both sexes. Oxytocin acts on pelvic autonomic neurons to increase genital blood flow and sensitivity through both parasympathetic and nitric oxide-mediated mechanisms.
Distinct from Peripheral Vasodilators
PT-141's mechanism is fundamentally different from PDE5 inhibitors. While sildenafil and tadalafil enhance peripheral genital blood flow by inhibiting PDE5 (downstream of NO signaling), PT-141 acts centrally to enhance sexual desire and the neurobehavioral components of arousal — it activates the brain circuits that initiate the sexual response cycle.
Biological Pathways
MC4R/Gαs/cAMP/PKA Central Signaling
MC4R activation couples to Gαs, increasing cAMP in hypothalamic neurons. PKA-mediated phosphorylation modulates ion channels and neurotransmitter release, enhancing excitatory signaling in sexual arousal circuits.
Dopamine/D1-D2 Reward Pathway
MC4R-mediated dopamine release activates D1 and D2 receptors in the nucleus accumbens and prefrontal cortex. D1 receptor activation enhances approach motivation, while D2 receptor signaling modulates reward sensitivity.
Oxytocin/PVN Autonomic Pathway
Paraventricular nucleus oxytocin neurons project to the spinal cord (sacral parasympathetic nuclei), activating pelvic nerve pathways that increase genital blood flow, lubrication, and tissue engorgement through NO-mediated vasodilation.
Endorphin/Opioid Modulation
MC4R signaling modulates endogenous opioid release, contributing to the pleasurable and rewarding aspects of sexual arousal. This interaction with the endogenous opioid system is part of the broader melanocortin-opioid axis in reward and motivation.
Dosage Information
Calculation Results
Syringe Fill Level (100u syringe)
Protocols
PT-141 Libido EnhancementBeginner🏃Sport & PerformanceAs needed
FDA-approved peptide for sexual dysfunction and libido enhancement. Works through nervous system.
Warning: Nausea common (take anti-nausea med if needed). Flushing and headache possible.
Stability & Storage
PT-141 (Vyleesi) is commercially available as a ready-to-use subcutaneous auto-injector containing 1.75 mg bremelanotide in 0.3 mL solution. Store at controlled room temperature (20-25°C). The commercial product has a shelf life of 2 years.
Research-grade PT-141 is supplied as lyophilized powder. Store at -20°C for long-term stability (18-24 months) or 2-8°C for up to 6 months. The cyclic structure provides enhanced protease resistance compared to linear peptides.
Reconstitute with bacteriostatic water. Store reconstituted solution at 2-8°C and use within 21-28 days. PT-141 is stable at physiological pH and is not significantly affected by light exposure.
Side Effects & Precautions
Nausea (Most Common)
Nausea is the most frequently reported adverse effect (40% in clinical trials), typically occurring 1-2 hours after injection and lasting 2-4 hours. Anti-emetic pretreatment may be helpful. The nausea is centrally mediated through MC4R activation in the area postrema.
Flushing
Facial and body flushing occurs in approximately 20% of users, related to melanocortin-mediated vasodilation. Usually transient (30-60 minutes).
Injection Site Reactions
Mild pain, redness, or bruising at injection site (13%). Typical for subcutaneous peptide administration.
Headache
Reported in approximately 11% of patients. Usually mild and self-limiting.
Transient Hypertension
PT-141 can transiently increase blood pressure by 5-10 mmHg for 6-12 hours post-injection. It is contraindicated in patients with uncontrolled hypertension or significant cardiovascular disease.
Skin Hyperpigmentation
Despite reduced MC1R activity compared to Melanotan II, some skin darkening can occur with repeated use, particularly in individuals with darker baseline skin tones. This is generally mild and reversible.
Dosing Limitation
FDA labeling recommends no more than one dose per 24 hours and no more than 8 doses per month to minimize cardiovascular and other side effects.
Research Use Only. This information is for educational and research purposes only. Not intended for medical advice or self-medication.
Regulatory Status
PT-141 (bremelanotide, Vyleesi) received FDA approval in June 2019 for the treatment of acquired, generalized HSDD in premenopausal women. It is marketed by Palatin Technologies/AMAG Pharmaceuticals. Available by prescription only as a 1.75 mg subcutaneous auto-injector.
The FDA approval was limited to premenopausal women with generalized HSDD (not situational or due to relationship issues, medical conditions, or medications). It carries contraindications for uncontrolled hypertension and a dosing limit of 8 injections per month.
WADA does not specifically list PT-141 on the prohibited list, though melanocortin agonists may fall under certain prohibited categories depending on interpretation. Athletes should verify current regulations.
Research Studies
Bremelanotide for Female Sexual Dysfunctions (RECONNECT Trials)
Kingsberg SA, Clayton AH, Pfaus JG.
Bremelanotide: New Drug for Hypoactive Sexual Desire Disorder
Simon JA, Kingsberg SA, Portman D, et al.
Melanocortin Receptor Agonists and Sexual Behavior
Pfaus JG, Shadiack A, Van Soest T, et al.
PT-141: A Melanocortin Agonist for Erectile Dysfunction
Diamond LE, Earle DC, Rosen RC, et al.
