What is PT-141?

PT-141, also called as Bremelanotide, is a derivative for Melanotan 2 (M2). Unlike M2, PT-141 lacks C-terminal amide molecules. PT-141, a synthetic cyclic hepta-peptide lactam derivative of alpha-Melanocyte-stimulating hormone (alpha-MSH), is an agonist at melanocortin receptors including the MC3R and MC4R, which are expressed primarily in the central nervous system. Melanocortin receptors are members of the rhodopsin family of 7-transmembrane G protein-coupled receptors. There are five known members of the melanocortin receptor system each with differing specificities for melanocortins: MC1R; MC2R; MC3R; MC4R; MC5R.


PT-141 was developed from the peptide hormone melanotan II which underwent testing as a sunless tanning agent. Sunless tanning, also known as UV-free tanning, self tanning, spray tanning (when applied topically), or fake tanning, refers to the application of chemicals to the skin to produce an effect similar in appearance to a suntan. In initial testing, melanotan II did induce the production of darkening dermal pigmentation (melanogenesis) but additionally caused sexual arousal and spontaneous erections as unexpected side effects in nine out of the ten original male volunteer test subjects. Due to this potential, PT-141 is being studied as a potential treatment for sexual disorders such as erectile disorders in men and sexual arousal disorders in women, especially Hypoactive sexual desire disorder (HSDD) and female sexual interest/arousal disorder (FSIAD). However, reports of elevated blood pressures halted the trial.

Hypoactive sexual desire disorder (HSDD) or inhibited sexual desire (ISD) is considered a sexual dysfunction and is characterized as a lack or absence of sexual fantasies and desire for sexual activity, as judged by a clinician. Female sexual arousal disorder (FSAD) is a disorder characterized by a persistent or recurrent inability to attain sexual arousal or to maintain arousal until the completion of a sexual activity. PT-141 is the only synthetic aphrodisiac. Unlike Viagra and other related medications (PDE5 inhibitors), PT-141 does not act upon the vascular system, but directly through the nervous system (hypothalamus) to increase desire. Viagra, Cials and Levitra are not considered aphrodisiacs as they do not have any direct effect on the libido. However, treatment with PDE5 inhibitors and PT-141 are known to have a synergistic effect. 


In a phase 2B trial, PT-141 was reformulated as a lower dose, subcutaneous injection to measure efficacy for HSDD and/or FSAD treatment in premenopausal women. In a 4-week at-home trial, 1.75 mg PT-141 showed statistically significant improvements as compared with placebo in five measures of FSD: number of satisfying sexual events per month, total and sexual domain scores on the FSFI, and total and desire domain scores on the FSDS. PT-141 was associated with minimal and transient increases in blood pressure (~3 mmHg) that were limited to the first four hours after administration. Protocol-defined blood pressure withdrawal criteria were not met at higher frequency in PT-141-treated subjects than in those taking placebo. Further studies on PT-141 dosing have suggested optimal increases in arousal, desire, and satisfaction with sexual events with 1.25 and 1.75 mg subcutaneous injections. At these doses, adverse events included nausea (22 % and 24 %, respectively), placebo 3 %; flushing (14 % and 17 %, respectively), placebo 0 %; and headache (9 % and 14 %, respectively), placebo 3 %. MC3R and MCR4 receptors are involved in many physiological systems and there may be theoretical risks of activating these receptors. The long-term effects of BMT are unknown.


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