Melanotan II (MT-II) is a synthetic cyclic heptapeptide analogue of α-melanocyte-stimulating hormone (α-MSH), developed at the University of Arizona as a candidate sunless-tanning and photoprotective agent.1 It is a non-selective agonist at melanocortin receptors, with activity reported at MC1R (pigmentation) and MC3R/MC4R (central effects).2 It is not an approved drug in Canada, the United States, or elsewhere, and is sold strictly for laboratory research use only. Human data are limited to a small pilot phase-I study and two small placebo-controlled crossover trials in erectile dysfunction.135 No phase 2 or phase 3 safety trial has been completed, and unregulated use has been associated with serious adverse events in case reports.6
Sequence & identity
Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH₂ · C₅₀H₆₉N₁₅O₉ · 1024.2 g/mol
Cyclic lactam-bridged heptapeptide. Structure and identifiers per PubChem CID 92432 (InChIKey JDKLPDJLXHXHNV-MFVUMRCOSA-N).2
Mechanisms studied
Researchers describe Melanotan II as a synthetic, metabolically stabilized cyclic analogue of α-MSH that acts as a potent non-selective melanocortin receptor agonist.12 At the melanocortin-1 receptor (MC1R) on melanocytes, agonism was reported to stimulate melanogenesis (eumelanin synthesis), which investigators proposed as the basis for the observed skin darkening that occurred without ultraviolet exposure.1 Activity at centrally expressed MC3R and MC4R has been invoked to explain the erectogenic and sexual-desire-modulating effects reported in the erectile-dysfunction studies; in those studies the erectile response was reported to occur largely independently of direct sexual stimulation.345 The compound was reported to be substantially more potent than native α-MSH in melanotropic bioassays.1
Dosing in the research literature
The figures below summarise regimens as reported in published research — they are not recommendations or directions for use.
| Source / model | Regimen reported | Notes |
|---|---|---|
| Dorr 1996, Life Sci (pilot phase-I)1 | 0.01 mg/kg subcutaneously, given on a Monday-through-Friday schedule across two weeks in healthy male volunteers | As reported in a single-blind, placebo-controlled pilot phase-I study (small n, 3 volunteers). Increased pigmentation was observed after roughly five low-dose injections. Reported as study procedures only — not usage directions. |
| Wessells 1998, J Urol (psychogenic ED)3 | 0.025 mg/kg as a single subcutaneous injection, double-blind placebo-controlled crossover (n=10) | Dose used in the cited erectile-dysfunction study; manageable side effects were reported at this dose. For research context only. |
| Wessells 2000, Urology (organic ED)5 | 0.025 mg/kg subcutaneously versus vehicle, double-blind placebo-controlled crossover (n=10) | RigiScan-monitored over a 6-hour period. Reported as study methodology, not a recommended regimen. |
Effects observed in research
In a pilot phase-I study, subcutaneous Melanotan II was reported to produce visible skin darkening (increased pigmentation of the face, upper body, and buttocks) in healthy volunteers without ultraviolet exposure.1 In a double-blind placebo-controlled crossover study in ten men with erectile dysfunction of no known organic cause, investigators reported clinically apparent erections in 8 of 10 men, with mean tip rigidity exceeding 80% lasting 38.0 minutes after Melanotan II versus 3.0 minutes after placebo.3 In a pooled report of the University of Arizona human studies, penile erection was reported in 17 of 20 men, and increased sexual desire was reported after 13 of 19 (68%) Melanotan II doses versus 4 of 21 (19%) placebo doses.4 A separate crossover study in men with organic erectile dysfunction reported subjective erections after 12 of 19 Melanotan II injections versus 1 of 21 placebo doses.5 Across these studies, the most frequently reported adverse effects were nausea, yawning, and stretching; at 0.025 mg/kg a subset of doses was associated with severe nausea.35 Separately, case reports from unregulated use describe new or changing atypical naevi and melanocytic lesions, and one report documented systemic toxicity with rhabdomyolysis and acute kidney injury following a single self-administered 6 mg injection.6
Strength of evidence
Grade B — limited human data. The human evidence consists of a single small pilot phase-I study1 and small (n≈10-20) placebo-controlled crossover studies in erectile dysfunction.345 No phase 2 or phase 3 trial has established efficacy or safety, so the true incidence of serious adverse events is not established. The melanoma and atypical-naevi associations come from individual case reports and cannot establish causation.6 Melanotan II is not an approved medicine in any jurisdiction and is supplied for research use only; the pigmentation and sexual-function findings above are reported observations from the cited studies, not endorsed uses.
Reconstitution & storage
Reconstitute with bacteriostatic water for laboratory handling. Store lyophilised material frozen and reconstituted material refrigerated. Use Peptigo’s reconstitution calculator and storage cheat sheet for working figures.
References
- Dorr RT, Lines R, Levine N, Brooks C, Xiang L, Hruby VJ, Hadley ME. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sci. 1996;58(20):1777-1784. doi:10.1016/0024-3205(96)00160-9. PMID:8637402.
- National Center for Biotechnology Information. PubChem Compound Summary for CID 92432, Melanotan II. InChIKey JDKLPDJLXHXHNV-MFVUMRCOSA-N; CAS 121062-08-6. https://pubchem.ncbi.nlm.nih.gov/compound/92432
- Wessells H, Fuciarelli K, Hansen J, Hadley ME, Hruby VJ, Dorr R, Levine N. Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: a double-blind, placebo controlled crossover study. J Urol. 1998;160(2):389-393. doi:10.1016/S0022-5347(01)62903-3. PMID:9679885.
- Wessells H, Levine N, Hadley ME, Dorr R, Hruby V. Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II. Int J Impot Res. 2000;12(Suppl 4):S74-S79. doi:10.1038/sj.ijir.3900582. PMID:11035391.
- Wessells H, Gralnek D, Dorr R, Hruby VJ, Hadley ME, Levine N. Effect of an alpha-melanocyte stimulating hormone analog on penile erection and sexual desire in men with organic erectile dysfunction. Urology. 2000;56(4):641-646. doi:10.1016/S0090-4295(00)00680-4. PMID:11018622.
- Nelson ME, Bryant SM, Aks SE. Melanotan II injection resulting in systemic toxicity and rhabdomyolysis. Clin Toxicol (Phila). 2012;50(10):1169-1173. doi:10.3109/15563650.2012.740637. PMID:23121206.