PT-141

Active sexual desire disorder (HSDD) is a persistent deficiency or absence of sexual
fantasies and desire resulting in significant distress or interpersonal difficulty. Women with this disorder
may display a lack of motivation for sexual activity, reduced responsiveness to erotic cues, a loss of
interest during sexual activity, and avoidance of situations that could lead to sexual activity. The
pathophysiology of HSDD is thought to be centered around inhibitory and excitatory hormones,
neurotransmitters, and specific brain anatomy. Due to the multifactorial nature of HSDD, treatment can
be complex and must attempt to target the biological and psychosocial aspects of the disorder.
Bremelanotide is a melanocortin receptor agonist and has been recently approved by the FDA to treat
HSDD. Bremelanotide is administered intranasally or as a subcutaneous injection. The recommended
dosage of bremelanotide is 1.75 mg injected subcutaneously in the abdomen or thigh at least 45 min
before sexual activity. Studies showed improvements in desire, arousal, and orgasm scores when 1.75
mg of bremelanotide was administered before sexual activity compared to a placebo. Bremelanotide is a
promising way to treat HSDD.
Reference:
Edinoff AN, Sanders NM, Lewis KB, Apgar TL, Cornett EM, Kaye AM, Kaye AD. Bremelanotide for
Treatment of Female Hypoactive Sexual Desire. Neurol Int. 2022 Jan 4;14(1):75-88. doi:
10.3390/neurolint14010006. PMID: 35076581; PMCID: PMC8788464.

PT-141, a synthetic peptide analogue of alpha-MSH, is an agonist at melanocortin receptors including
the MC3R and MC4R, which are expressed primarily in the central nervous system. Administration of PT141 to rats and nonhuman primates results in penile erections. Systemic administration of PT-141 to rats
activates neurons in the hypothalamus as shown by an increase in c-Fos immunoreactivity. Neurons in
the same region of the central nervous system take up pseudorabies virus injected into the corpus
cavernosum of the rat penis. Administration of PT-141 to normal men and to patients with erectile
dysfunction resulted in a rapid dose-dependent increase in erectile activity. The results suggest that PT141 holds promise as a new treatment for sexual dysfunction.
Reference:
Molinoff PB, Shadiack AM, Earle D, Diamond LE, Quon CY. PT-141: a melanocortin agonist for the
treatment of sexual dysfunction. Ann N Y Acad Sci. 2003 Jun;994:96-102. doi: 10.1111/j.1749-
6632.2003.tb03167.x. PMID: 12851303.