PT-141
Also known as: Bremelanotide, Vyleesi
PT-141 (Bremelanotide) is a synthetic peptide that acts on melanocortin receptors. It was developed from the tanning peptide Melanotan II and has been studied for sexual dysfunction.
PT-141 Overview & Molecular Profile
PT-141 is a cyclic heptapeptide melanocortin receptor agonist derived from Melanotan II. Unlike phosphodiesterase inhibitors, PT-141 works through the nervous system rather than the vascular system. It received FDA approval in 2019 under the brand name Vyleesi for treating hypoactive sexual desire disorder in premenopausal women.
Mechanism of Action: Receptor Agonism & Metabolic Pathways
PT-141 acts as an agonist at melanocortin receptors, particularly MC3R and MC4R, in the central nervous system. These receptors are involved in sexual function and arousal. By activating these pathways, PT-141 affects sexual response through central mechanisms rather than peripheral vascular effects.
Research-Observed Effects
Sexual Function Research
Extensive clinical research on PT-141 for sexual dysfunction treatment has demonstrated significant improvements in sexual desire and arousal through central melanocortin receptor activation in the hypothalamus and limbic system. Phase 3 clinical trials involving over 1,200 premenopausal women with hypoactive sexual desire disorder (HSDD) showed statistically significant increases in satisfying sexual events and reductions in distress related to low sexual desire compared to placebo groups. Unlike phosphodiesterase type 5 (PDE5) inhibitors that work through vascular mechanisms, PT-141 operates through the central nervous system, making it effective for desire-related sexual dysfunction research rather than purely mechanical arousal issues. Studies have documented onset of effects within 30-60 minutes following subcutaneous administration, with effects lasting up to 24 hours in some research subjects. These findings have positioned PT-141 as a unique research compound for investigating neural pathways involved in female sexual dysfunction treatment, male erectile dysfunction research, and understanding the neurobiological basis of sexual motivation and arousal.
Melanocortin Pathway Activation
Research demonstrates PT-141's potent agonist activity at melanocortin-3 (MC3R) and melanocortin-4 (MC4R) receptors, which are critical G-protein coupled receptors involved in regulating sexual behavior, energy homeostasis, and autonomic nervous system function. Binding studies show PT-141 has high affinity for MC4R with EC50 values in the nanomolar range, triggering intracellular signaling cascades that activate cyclic AMP and protein kinase A pathways in hypothalamic neurons. The peptide's cyclic structure, derived from its parent compound Melanotan II, provides enhanced metabolic stability and receptor selectivity compared to linear melanocortin analogs. Research into melanocortin receptor agonist mechanisms has revealed that MC4R activation in the paraventricular nucleus directly influences sexual arousal pathways independent of peripheral hormonal changes. These melanocortin pathway studies have significant implications for understanding central regulation of sexual function, appetite control mechanisms, and potential therapeutic targets for metabolic and reproductive disorders.
Central Nervous System Effects
Neuroimaging and behavioral studies indicate PT-141 produces significant central nervous system effects on motivation, reward processing, and emotional regulation through melanocortin receptor activation in limbic structures. Functional MRI research has shown increased activity in brain regions associated with sexual arousal and desire following PT-141 administration, including the anterior cingulate cortex and insula. Studies demonstrate the peptide's effects are mediated through descending neural pathways from the hypothalamus to the spinal cord, influencing both autonomic and somatic components of sexual response. Research has documented effects on dopaminergic neurotransmission, with PT-141 potentially modulating dopamine release in reward-related brain circuits. These CNS-mediated effects distinguish PT-141 from peripheral-acting sexual dysfunction treatments and have generated interest in its potential applications for research into depression-related sexual dysfunction, motivational disorders, and understanding the neuroscience of desire and reward processing.
Research Dosing Information
FDA-approved dosing for Vyleesi is 1.75 mg subcutaneous injection. Research studies have used various dosages. Intranasal formulations have also been studied.
Note: Dosing information is provided for research reference only and is based on published studies using research subjects. This is not a recommendation for any use.
Research Studies & References
Bremelanotide for Female Sexual Dysfunctions in Premenopausal Women
Kingsberg SA, Clayton AH, et al. (2019). Obstetrics & Gynecology
This pivotal Phase 3 clinical trial evaluated bremelanotide (PT-141) efficacy and safety in premenopausal women with hypoactive sexual desire disorder (HSDD), ultimately leading to FDA approval. The randomized, double-blind, placebo-controlled RECONNECT studies enrolled over 1,200 women who self-administered 1.75 mg subcutaneous injections as needed before anticipated sexual activity for 24 weeks. Results demonstrated statistically significant improvements in the Female Sexual Function Index desire domain score and meaningful reductions in distress associated with low sexual desire as measured by the Female Sexual Distress Scale. Approximately 25% of treatment subjects achieved clinically meaningful response compared to 17% with placebo, with effects observed as early as 4 weeks into treatment. The study established PT-141's unique mechanism as the first FDA-approved treatment for HSDD that works through central nervous system melanocortin pathways rather than hormonal manipulation, representing a significant advancement in sexual dysfunction research and women's health therapeutics.
Melanocortin receptor agonists, penile erection, and sexual motivation
Wessells H, Fuciarelli K, et al. (2005). Annals of the New York Academy of Sciences
This comprehensive review and research study examined PT-141's effects on male sexual function through melanocortin receptor activation, establishing the mechanistic basis for its pro-erectile effects independent of vascular changes. Researchers demonstrated that subcutaneous PT-141 administration induced penile erection in healthy men through central nervous system pathways, with effects occurring even in the absence of sexual stimulation. The study documented dose-dependent increases in erectile response and sexual arousal scores, with optimal effects observed at doses between 4-6 mg in early clinical investigations. Neurophysiological analysis confirmed that PT-141's effects were mediated through supraspinal mechanisms rather than direct penile vascular effects, distinguishing it from PDE5 inhibitors. These findings established the foundation for understanding melanocortin-based approaches to erectile dysfunction treatment and identified PT-141 as a valuable research tool for investigating central control of male sexual function.
Central melanocortin signaling and sexual function
Van der Ploeg LH, Martin WJ, et al. (2002). Current Opinion in Pharmacology
This foundational review synthesized early research on melanocortin receptor signaling in sexual function, providing the theoretical framework for PT-141 development as a sexual dysfunction treatment. The authors analyzed preclinical evidence demonstrating that MC3R and MC4R activation in the hypothalamus and limbic system directly influences sexual arousal, desire, and copulatory behavior in multiple species. Research presented showed that melanocortin agonists increase lordosis in female rodents and penile erection in male models through activation of oxytocinergic neurons in the paraventricular nucleus. The review highlighted the unique advantage of targeting central melanocortin pathways for addressing desire-related sexual dysfunction rather than purely mechanical arousal issues addressed by peripheral vasodilators. These mechanistic insights guided subsequent clinical development of PT-141 and established melanocortin receptors as validated therapeutic targets for sexual medicine research.