PT-141
Bremelanotide
Non-selective melanocortin receptor agonist
About PT-141
PT-141 (bremelanotide) is a synthetic cyclic heptapeptide analog of alpha-melanocyte-stimulating hormone (α-MSH), derived from melanotan II.
It non-selectively activates several melanocortin receptors; according to the FDA label, at therapeutic doses the most relevant are MC1R and MC4R, the latter present in many areas of the central nervous system. Unlike PDE5 inhibitors, which act on vascular flow, it is studied for its central action on pathways involved in sexual desire and arousal; the label states that the mechanism by which it improves hypoactive sexual desire disorder is unknown. It has been approved by the FDA since 2019 (Vyleesi®) for acquired, generalized hypoactive sexual desire disorder in premenopausal women.
Quick guide · 5 key points
PT-141 and men's sexual health
Most options act on blood flow. PT-141 acts on the brain pathways that drive desire and arousal. Here are five things the research shows.
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1
It works in the brain, not just the blood vessels
PT-141 is a non-selective melanocortin receptor agonist; according to the FDA label, MC1R and MC4R are the most relevant at therapeutic doses. MC4R is expressed mainly in the central nervous system; in rats, PT-141 activated neurons in the hypothalamus. MC4R has been found in the rat hypothalamus and spinal cord and in nerve fibers of the human glans. The label states that its mechanism in hypoactive sexual desire disorder is unknown.1,2,7
PDE5 inhibitorsViagra®, Cialis® widen blood vessels. Arousal has to come first.PT-141Acts on central nervous system receptors, in pathways involved in desire and arousal.MC4RReceptor involved in erectile function in animal studies -
2
Measurable erections, with a fast onset
In placebo-controlled studies in men, PT-141 has been associated with statistically significant erectile responses measured by RigiScan®. In healthy men this was seen even without visual sexual stimulation.3
~30 minTime to first erection after a nasal dose -
3
A response when Viagra® falls short
In men who had an inadequate response to 100 mg Viagra® (a usable erection half the time or less), subcutaneous PT-141 has been associated with significant erectile responses compared with placebo. The authors suggest that, because it works on a different pathway, it could be an alternative for men who don't respond to PDE5 inhibitors.4
2 pathwaysPT-141 doesn't rely on the same mechanism as Viagra® -
4
Combined with low-dose sildenafil
In a crossover study in 19 men with erectile dysfunction, a low dose of intranasal PT-141 with a low dose of sildenafil has been associated with a significantly greater erectile response than sildenafil alone, with no new adverse events and none more frequent or severe than with monotherapy.5
19Men in the crossover study of low-dose PT-141 + sildenafil -
5
An FDA-approved molecule with known side effects
Bremelanotide was approved by the FDA in 2019 (Vyleesi®) for acquired, generalized hypoactive sexual desire disorder in premenopausal women, after two phase 3 trials in more than 1,200 participants showed improved desire. It is not approved for use in men. According to the label, the most common adverse reactions are nausea, flushing, injection-site reactions, headache and vomiting. According to the label, blood pressure rises transiently after each dose, and focal hyperpigmentation has been reported.6,3,7
2019FDA approval, after phase 3 trials with 1,200+ participants
References
- Van der Ploeg LH, et al. A role for the melanocortin 4 receptor in sexual function. Proc Natl Acad Sci USA. 2002;99(17):11381-6. PMID 12172010
- Molinoff PB, et al. PT-141: a melanocortin agonist for the treatment of sexual dysfunction. Ann N Y Acad Sci. 2003;994:96-102. PMID 12851303
- Diamond LE, et al. Double-blind, placebo-controlled evaluation of the safety, pharmacokinetic properties and pharmacodynamic effects of intranasal PT-141, a melanocortin receptor agonist, in healthy males and patients with mild-to-moderate erectile dysfunction. Int J Impot Res. 2004;16(1):51-9. PMID 14963471
- Rosen RC, et al. Evaluation of the safety, pharmacokinetics and pharmacodynamic effects of subcutaneously administered PT-141, a melanocortin receptor agonist, in healthy male subjects and in patients with an inadequate response to Viagra. Int J Impot Res. 2004;16(2):135-42. PMID 14999221
- Diamond LE, et al. Co-administration of low doses of intranasal PT-141, a melanocortin receptor agonist, and sildenafil to men with erectile dysfunction results in an enhanced erectile response. Urology. 2005;65(4):755-9. PMID 15833522
- Kingsberg SA, et al. Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials. Obstet Gynecol. 2019;134(5):899-908. PMID 31599840
- U.S. Food and Drug Administration. Vyleesi (bremelanotide injection) prescribing information. NDA 210557, 2019. Official source
Structure and sequence
Sequence
Five findings from studies
Summary of results reported in the scientific literature. Each finding describes what was observed in the cited study, in its specific population and conditions; it does not constitute a therapeutic indication.
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Clinical study
In the phase 3 RECONNECT trials (more than 1,200 premenopausal women with hypoactive sexual desire disorder), an improvement in sexual desire and a reduction in associated distress versus placebo have been shown.
Kingsberg SA et al. Obstet Gynecol. 2019;134:899-908 · PMID 31599840 -
Regulatory
Bremelanotide has received FDA approval (2019) for acquired, generalized hypoactive sexual desire disorder in premenopausal women.
FDA. Vyleesi (bremelanotide) — prescribing information, NDA 210557 -
Clinical study
In healthy men and in men with mild-to-moderate erectile dysfunction, intranasal PT-141 has been associated with an erectile response significantly greater than placebo at doses above 7 mg.
Diamond LE et al. Int J Impot Res. 2004;16:51-59 · PMID 14963471 -
Clinical study
In men with erectile dysfunction and an insufficient response to sildenafil, subcutaneous PT-141 has been associated with an erectile response significantly greater than placebo.
Rosen RC et al. Int J Impot Res. 2004;16:135-142 · PMID 14999221 -
Clinical study
In a phase 2b trial (327 premenopausal women), improvements in satisfying sexual events and in overall sexual function, and a reduction in distress, have been observed versus placebo.
Clayton AH et al. Womens Health (Lond). 2016;12:325-337 · PMID 27181790
