PT-141 or bremelanotide is a partial (hexapeptide) analog of alpha-melanocyte stimulating hormone (a-MSH), originally developed from the melanotropin peptide melanotan-II (MT2). Bremelanotide was conceived as treatment for sexual arousal disorders for men and women without any pigmentation effects; the primary action of PT-141 is mediated through the first and fourth melanocortin receptors (MC1R and MC4R).
PT-141 induces lordosis (physical preparation for reproduction) in animal models, and in humans stimulates the central nervous system (CNS) primarily via downstream dopamine receptor activity, increasing sexual desire and in some cases improving physical erectile dysfunction despite the fact it does not stimulate the vascular function of the penis directly.
Bremelanotide has been studied in double-blind placebo controlled studies using both intranasal and subcutaneous (including implants) administration; route of administration was the most significant factor in adverse events, with "variability of uptake" after intranasal administration of the peptide causing "increases in blood pressure and gastrointestinal events...primarily related to high plasma levels in [only] a subset of patients".
The similarity in mechanisms-of-action of currently available (FDA-approved) medical treatments for ED means medical practitioners are often limited in treating patients who do not respond well to that class (PDE5 inhibitor) of drug.
Erectile dysfunction is multifaceted, but most drugs currently approved work through a similar mechanism; PT-141 can be used in conjunction with PDE5 inhibitors, and may work in cases where they do not. As Hellstrom (2008) writes:
Currently available agents for erectile dysfunction (ED) share the same mechanism of action and pharmacologic properties. Therefore, they share the same limitations, including a principal focus on erection as an end-organ process. One of the relatively unexplored areas of research has been the potential for centrally acting agents to improve male sexual response. A variety of neurohormones and neurotransmitter systems are involved in the male sexual response, including testosterone, dopamine, serotonin and the melanocortin systems. Investigations to determine the utility of centrally acting agents as monotherapy or adjunctive therapy in men with ED or other forms of sexual dysfunction are underway. Bremelanotide, a melanocortin agonist, has been tested in men with ED and may prove to be one of the first centrally acting agents to have clinical utility in male sexual dysfunction.
Unlike other approved drugs for sexual dysfunction, bremelanotide also has traits that increase its potential efficacy for female use. In women (as compared to men), genital dysfunction is more often paired with lack of desire. Diamond et al (2006) in a study designed 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", found the following:
More women reported moderate or high sexual desire following bremelanotide treatment vs. placebo..., and a trend toward more positive responses regarding feelings of genital arousal occurred after bremelanotide compared with placebo.... 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 .... Vaginal vasocongestion did not change significantly while viewing erotic videos following bremelanotide administration compared with placebo.
The researchers also concluded that an at-home study would better demonstrate the real-world efficacy of bremelanotide for treatment of female sexual arousal/desire disorders.
In men with erectile dysfunction who did not respond to sildenafil, PT-141 worked four times better than placebo (33% vs 8%).
In severe cases, Diamond et al (2005) found that “co-administration of PT-141 and sildenafil was safe and well-tolerated and did not result in new adverse events or adverse events that were increased in frequency or severity compared with monotherapy…Co-administration of intranasal PT-141 and a phosphodiesterase type 5 inhibitor may constitute a treatment alternative for patients in whom higher doses of a single therapy are not effective or well tolerated”.
 Palatin Technologies: Bremelanotide Overview. (Available online:http://www.palatin.com/products/bremelanotide/overview.asp). Accessed 3-24-2016.
Hellstrom WJ. Clinical applications of centrally acting agents in male sexual dysfunction. Int J Impot Res. 2008 Jul;20 Suppl 1:S17-23.
Palatin Technologies Inc. Press Release. “Palatin Technologies, Inc. Reports Positive Bremelanotide Study; Improved Safety Profile with Subcutaneous Administration.” 8-12-2009, accessed 3-24-2016. (Available online: http://www.prnewswire.com/news-releases/palatin-technologies-inc-reports-positive-bremelanotide-study-improved-safety-profile-with-subcutaneous-administration-62211132.html)
Diamond LE, Earle DC, Heiman JR, Rosen RC, Perelman MA, Harning R. An effect on the subjective sexual response in premenopausal women with sexual arousal disorder by bremelanotide (PT-141), a melanocortin receptor agonist. J Sex Med. 2006 Jul;3(4):628-38.
Safarinejad MR, Hosseini SY. Salvage of sildenafil failures with bremelanotide: a randomized, double-blind, placebo controlled study. J Urol. 2008 Mar;179(3):1066-71.
Diamond LE, Earle DC, Garcia WD, Spana C. 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 Apr;65(4):755-9.