Overview
Following subcutaneous injection, MT-II has a short plasma half-life of approximately 30–60 minutes due to peptidase activity, but its biological effects (particularly pigmentation) outlast its presence in circulation due to downstream transcriptional changes. Peak plasma concentration is achieved within 30–90 minutes subcutaneously. The peptide crosses the blood-brain barrier poorly in physiological conditions but exerts CNS effects likely via circumventricular organs and median eminence fenestrated capillaries. Hepatic metabolism and renal excretion are the primary clearance routes. Bioavailability via intranasal route is substantially lower (~5–10%) than subcutaneous (~90%), explaining the large dose discrepancy in commercial nasal formulations.
Proposed mechanism
MT-II acts as a non-selective agonist at melanocortin receptors MC1R, MC3R, MC4R, and MC5R. Activation of MC1R on melanocytes upregulates cAMP production via Gs protein coupling, driving tyrosinase activity and eumelanin synthesis for UV-independent skin darkening. Simultaneous MC4R activation in hypothalamic nuclei mediates appetite suppression and pro-erectile signaling through downstream nitric oxide pathways.
What the evidence supports
Human data exists but the trials are small, short-term, or not yet replicated.
Graded Human-limited
Human data that exists but is thin: open-label work, single-arm studies, small cohorts, or observational follow-up without randomisation.
Key citations
Representative primary sources, including results that did not favour the compound.
- [1]
Hadley ME, Dorr RT. Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization
· Peptides 27(4):921-30. DOI: 10.1016/j.peptides.2005.01.029 · 2006
- [2]
Wessells H, et al. Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study
· Journal of Urology 160(2):389-93. DOI: 10.1016/S0022-5347(01)62898-9 · 1998
- [3]
Langan EA, et al. Melanotropic peptide use and possible association with melanoma
· British Journal of Dermatology 161(5):1187-8. DOI: 10.1111/j.1365-2133.2009.09336.x · 2009
- [4]
Raposinho PD, et al. Melanocortin-4 receptor agonism causes weight loss via a mechanism involving mechanisms in the hypothalamic-pituitary axis
· Neuroendocrinology 78(1):1-9 · 2003
Citation records in this build are illustrative placeholders for the design.
Reference information for research purposes. Not medical advice, and not a recommendation to use any compound. Many entries describe substances that are not approved for human use.