PT-141 (bremelanotide) — pharmacology
Molecular targets, mechanism of action, pharmacokinetics and interactions as characterised in humans.
§2Pharmacology
§2.1Molecular targets
Table 2. Molecular targets recorded for PT-141 (bremelanotide), with the character of the interaction and the potency where the Institute holds it.
| Target | Interaction | Note |
|---|---|---|
| Melanocortin-4 receptor (MC4R) | Agonist | The receptor mediating the sexual-desire effect |
| Melanocortin-1 receptor (MC1R) | Agonist | Mediates pigmentary effects; hyperpigmentation is a recognised adverse effect |
| Melanocortin-3 and -5 receptors | Agonist | Non-selective across the family |
§2.2Mechanism of action
Bremelanotide activates central melanocortin-4 receptors, acting on hypothalamic and limbic circuits regulating sexual desire. Unlike phosphodiesterase-5 inhibitors it does not act on the peripheral vasculature. Its non-selectivity across the melanocortin family accounts for the pigmentary and cardiovascular effects seen in the class.[1,2]
§2.3Pharmacokinetics
- Terminal half-life
- ≈2.7 h
- Time to maximum concentration
- ≈1 h
- Volume of distribution
- ≈25.0 L
- Plasma protein binding
- ≈21 %
- Clearance
- ≈6.5 L/h
- Bioavailability
- ≈100 % (subcutaneous)
Hydrolysis to peptide fragments with renal and faecal excretion. Not a cytochrome P450 substrate.
§2.4Interactions
- Naltrexone — oral naltrexone exposure is reduced by delayed gastric emptying
- Oral medicines requiring rapid absorption may be affected
References cited on this page
References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.
- Clayton AH, Althof SE, Kingsberg S, DeRogatis LR, Kroll R, Goldstein I, Kaminetsky J, Spana C, Lucas J, Jordan R, Portman DJ. Bremelanotide for female sexual dysfunctions in premenopausal women: a randomized, placebo-controlled dose-finding trial. Women’s Health 2016;12(3):325–337. doi:10.2217/whe-2016-0018 · PMID 27638896
- D’Hondt M, Bracke N, Taevernier L, Gevaert B, Verbeke F, Wynendaele E, De Spiegeleer B. Related impurities in peptide medicines. Journal of Pharmaceutical and Biomedical Analysis 2014;101:2–30. doi:10.1016/j.jpba.2014.06.012 · PMID 25044089
Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.