Pharmacology
Pharmacodynamics
Bremelanotide is a non-selective agonist of the melanocortin receptors, MC1 through MC5 (with the exception of MC2, the receptor of ACTH), but acting primarily as an MC3 and MC4 receptor agonist. Pharmacokinetics
The bioavailability of bremelanotide with subcutaneous injection is about 100%. Following a subcutaneous injection of bremelanotide, maximal levels occur after about one hour, with a range of 0.5 to 1.0 hours. The plasma protein binding of bremelanotide is 21%. Bremelanotide is metabolized via hydrolysis of its peptide bonds. The elimination half-life of bremelanotide is 2.7 hours, with a range of 1.9 to 4.0 hours. Bremelanotide is excreted 64.8% in urine and 22.8% in feces. Chemistry
Bremelanotide is a cyclic heptapeptide lactam analogue of α-melanocyte-stimulating hormone (α-MSH). It has the amino acid sequence Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH, and is also known as cyclo-[Nle4,Asp5,D-Phe7,Lys10]α-MSH-(4-10). Bremelanotide is an active metabolite of melanotan II that lacks the C-terminal amide group.Aside from melanotan II and endogenous melanocyte-stimulating hormones like α-MSH, other peptide analogues of the same family as bremelanotide include afamelanotide (NDP-α-MSH), modimelanotide, and setmelanotide. History
Studies in the early 1960s showed that administration of α-MSH caused sexual arousal in rats, sparking interest in α-MSH. In the 1980s, scientists at University of Arizona began developing α-MSH and analogs as potential sunless tanning agents.
Contraindications
Due to its effects on blood pressure (generally a transient increase in systolic blood pressure by 6 mmHg, and diastolic blood pressure by 3 mmHg), bremelanotide is considered contraindicated in people with uncontrolled high blood pressure or cardiovascular disease. As long as bremelanotide is not used more than once in one day, it is not expected to cause more severe increases in blood pressure. Side effects
The most frequently encountered side effect of bremelanotide is nausea (40.0%), which may be intolerable to some people. The use of anti-nausea medications (e.g. ondansetron) prior to administration of bremelanotide may help to reduce the nausea. Other side effects may include flushing (20.3%), injection site reactions (13.2%), headache (11.3%), vomiting (4.8%), cough (3.3%), fatigue (3.2%), hot flushes (2.7%), paresthesia (2.6%), dizziness (2.2%), and nasal congestion (2.1%). Discoloration of the skin, specifically hyperpigmentation, may occur—especially if bremelanotide is used more than eight times in one month. The discoloration may not resolve upon stopping use of bremelanotide, and may occur on the face, gums, or breasts. Experiments in animals, even at high doses, failed to find any negative consequence of bremelanotide on fertility. Interactions
Bremelanotide does not meaningfully interact with alcohol, unlike flibanserin (for which the interaction with alcohol is a major barrier to its use). However, bremelanotide does interact with certain medications that people take by mouth. By slowing gastric motility, bremelanotide is thought to reduce the oral absorption (bioavailability) of certain medications, such as naltrexone and indomethacin.