What Is PT-141?
PT-141, also called bremelanotide, is sometimes referred to as the female Viagra because the peptide was previously investigated in phase IIb human clinical trials for use in treating female hypoactive sexual desire disorder (HSDD). PT-141 is a melanocortin that binds primarily to melanocortin 4 receptor (MC-4R) and MC-1R. In 2009, PT-141 was also investigated as a treatment for acute hemorrhage. PT-141 is a derivative of another synthetic melanocortin, melanotan 2 (MT-2).
PT-141 and Sexual Arousal
PT-141 is a unique peptide in that it stimulates the MC-4R, which is known to produce sexual arousal in the central nervous system and influence sexual behavior. Studies in mice have shown that agonist binding to MC-4R causes sexual arousal and increased copulation in both males and females. Because PT-141 works via a different mechanism than drugs like Viagra, it is possible to treat sexual arousal disorders in both men and women that stem from causes other than reduced blood flow to the genitals.
A study of men with erectile dysfunction (ED) who did not respond to sildenafil (Viagra) found that roughly one third experienced adequate erection for sexual intercourse with PT-141 (administered via nasal spray). There was also a strong dose-dependent response in the trial, indicating that PT-141 is indeed effective in certain cases. This suggests that PT-141 could offer insight into correcting ED in settings where sildenafil has failed and may offer insight into central causes of hypoactive sexual desire.
PT-141 and Hemorrhage
In 2009, PT-141 was modified slightly and investigated as a potential treatment for hemorrhagic shock. Because PT-141 binds to both MC-1R and MC-4R, it reduces ischemia and protects tissues against inadequate blood supply in the setting of hypovolemic (hemorrhagic) shock. The drug, when administered intravenously, does not produce substantial side effects. It was last in phase IIb trials. The modified version of PT-141 is referred to as PL-6983.
PT-141 and Infection
The MC-1R has been found, in a rat model of a specific fungal infection, to possess important anti-fungal and anti-inflammatory properties. This is of particular importance because current anti-fungals are limited in terms of their mechanism of action and all produce serious and treatment-limiting side effects in certain patients. Having an alternative to use in the treatment of fungal infections could reduce morbidity and mortality substantially, especially in patients with immune compromise.
PT-141 and Cancer
The MC-1R receptor is an important stimulus of DNA repair pathways and thus is of interest in cancer treatment and prevention. Research shows that people with variants of MC-1R are at increased risk for both basal cell and squamous cell carcinoma. Altered PT-141 may be able to correct the problems experienced as a result of these variants and prevent or treat these cancers.
PT-141 and Weight Loss
Research shows that the MC-4R plays a critical role in appetite regulation. Peptides like melanotan 2 and PT-141, which are agonists of the MC-4R, promote feelings of satiety and decrease total calorie intake. It appears that PT-141 also interacts with leptin signaling pathways to regulate food intake in a complex manner. This should not come as a surprise given that PT-141 is a derivative of α-MSH, which has been found to negatively regulate food intake via interactions with the ghrelin-leptin system.