+Melanocortin receptor agonist
+Female hypoactive sexual desire disorder
+Bremelanotide is the first-in-class MCR agonist and the second drug FDA approved for acquired HSDD in premenopausal women. It was preceded to market by flibanserin, an orally administered multifunctional serotonin agonist/antagonist.86 HSDD is characterized by a distressing absence of sexual desire not attributable to any identifiable cause.30,87 Bremelanotide is a synthetic neuropeptide analogue of alpha melanocyte-stimulating hormone.87 It nonselectively activates five MCR subtypes (MC1R–MC5R) and is thought to modulate brain pathways involved in sexual responsiveness, with activation of MC4R-expressing neurons (present in many areas of the central nervous system) and MC1R (expressed on melanocytes) thought to be the most clinically relevant.30,87
+Bremelanotide is marketed as an autoinjector for subcutaneous administration, as needed, at least 45 minutes before anticipated sexual activity, but not more than eight times per month.30 Repeat doses should be separated by at least 24 hours, and therapy should not be continued beyond 8 weeks unless symptom improvement is achieved.30 Bremelanotide may increase blood pressure and reduce heart rate for as long as 12 hours after administration.30 Patients with uncontrolled hypertension or high-risk cardiovascular disease are inappropriate for bremelanotide therapy.30 Bremelanotide is not recommended for use during pregnancy.30 Also, due to a reduction in systemic exposure, patients on oral naltrexone therapy are unsuitable candidates for bremelanotide therapy.30 Binding of bremelanotide to MC1R on melanocytes stimulates off-target hyperpigmentation, most notable on the face, gums, and breasts.30 Other premarket unwanted effects included nausea (40%, with 13% of study subjects requiring antiemetics), flushing (20%), injection site reactions (13%), and headache (11%).30,87 One premarket case of acute hepatitis has been reported.30 Bremelanotide slows gastric emptying and may interfere with concomitantly administered oral medications (e.g., antibiotics and rapid-onset pain medications).30
+The chemical structure of bremelanotide is shown in Figure P1–1. Peak plasma levels are reached within 30–60 minutes of dosing, and clearance of the 7–amino acid cyclic peptide is mainly through hydrolysis with urinary excretion.30 The mean terminal half-life is approximately 2.7 hours; however, the duration of the aphrodisiac effect is unknown.30 Bremelanotide was studied in two 24-week, phase 3, randomized, double-blind, placebo-controlled trials (NCT0233307188 and NCT0233896089).30 FDA approval was based on statistically significant increases over baseline, versus placebo, in patient scores of positive feelings of sexual desire and reductions in negative feelings of distress (as assessed by a standardized questionnaire) among a total of 595 subjects who received active therapy.30 Other melanocortin receptor agonists are in development, and several commentaries regarding the limits and challenges of a pure pharmacological approach to women with HSDD have been published.90–92
Further Reading in Goodman & Gilman
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