Melanotan II

Melanotan II (MT-II) is a synthetic cyclic heptapeptide analogue of alpha-melanocyte-stimulating hormone (alpha-MSH), developed at the University of Arizona in the late 1980s (molecular formula C50H69N15O9; MW approximately 1024 g/mol; CAS 121062-08-6).

MT-II acts as a non-selective agonist at four of the five known melanocortin receptor subtypes.

• MC1R activation on cutaneous melanocytes stimulates adenylyl cyclase via Gs-protein coupling, elevating intracellular cyclic AMP and upregulating tyrosinase. This shifts melanogenesis toward eumelanin (brown-black pigment), producing skin darkening that can occur independent of ultraviolet radiation.

• MC4R (and possibly MC3R) activation in hypothalamic and limbic circuits mediates sexual arousal and erection, modulating downstream dopaminergic and oxytocinergic pathways.

• MC3R and MC4R engagement in hypothalamic energy-regulation circuits produces the appetite suppression documented in animal and human studies.

• MC5R stimulation affects exocrine glands and likely contributes to flushing and autonomic responses observed after dosing.

This non-selective receptor profile contrasts with afamelanotide (Scenesse), the FDA-approved structural analogue that is substantially selective for MC1R and was approved in 2019 for erythropoietic protoporphyria. The broad receptor engagement of MT-II is the mechanistic source of its wider and more variable adverse-effect profile.

The primary human evidence for MT-II derives from a small research programme at the University of Arizona in the 1990s.

A 1996 Phase I pilot study (Dorr et al., Life Sciences 58(20):1777-84; DOI 10.1016/0024-3205(96)00160-9) enrolled three healthy male volunteers who received subcutaneous MT-II at doses escalating from 0.01 to 0.03 mg/kg on alternating weekdays over two weeks. Two of three subjects showed quantifiable increases in skin pigmentation by reflectance spectrometry one week after dosing ended. Dose-limiting adverse effects at 0.03 mg/kg included grade II somnolence, nausea, and spontaneous penile erections, the latter prompting a dedicated erectile function research programme.

Wessells and colleagues (Journal of Urology, 1998) conducted a double-blind, placebo-controlled crossover study in 10 men with psychogenic erectile dysfunction using MT-II 0.025 mg/kg subcutaneously. Eight of 10 subjects developed clinically apparent erections, with mean tip rigidity above 80% lasting 38.0 minutes on MT-II versus 3.0 minutes on placebo.

A second crossover trial by Wessells et al. (Urology, 2000; PMID 11018622) enrolled 10 men with organic erectile dysfunction; erections occurred after 12 of 19 active injections versus 1 of 21 placebo injections, with mean tip rigidity above 80% of 45.3 versus 1.9 minutes. Severe nausea occurred in 4 of 19 active sessions.

No Phase III trials were ever completed for any indication and no regulatory submission was made for tanning or erectile dysfunction. Animal research demonstrates MT-II suppresses food intake and body weight via hypothalamic MC3R and MC4R pathways, but these findings have not been translated into human efficacy trials.

Typical dosage: 250-500 mcg (as needed).

Published clinical research used subcutaneous doses of 0.025 mg/kg per injection, approximately 1.75 mg in a 70 kg subject. The 1996 Phase I study escalated doses from 0.01 to 0.03 mg/kg on alternating weekdays over two weeks; the Wessells erectile dysfunction trials used a single monitored bolus per laboratory session.

MT-II has no approved prescribing information in any jurisdiction. Community use, documented extensively in lay and commercial sources, typically describes a loading phase of 0.25-0.5 mg subcutaneously on a daily or alternating-day schedule for two to three weeks, followed by a maintenance phase of 0.5-1 mg once or twice weekly to sustain pigmentation. A widely cited community convention caps the single dose at 2 mg. Reconstitution is from lyophilised powder using bacteriostatic water; injection is typically subcutaneous to the abdomen or thigh. Community sources note that nausea and flushing are most prominent during the loading phase and tend to diminish with continued use.

This information is provided solely for educational reference and does not constitute medical advice. Melanotan II is not approved by any regulatory agency, has no established safe or effective dose range validated in regulated clinical trials, and carries poorly quantified risks when used outside a monitored clinical setting.

Lyophilized (before reconstitution)

Multiple vendor sources cite roughly 24 months at −20°C for Melanotan II lyophilized powder; up to 6 months refrigerated (2–8°C). Keep dry, sealed, and away from light — the peptide contains residues that are moderately light-sensitive.

Reconstituted

Commonly cited at ~28 days refrigerated (2–8°C) in bacteriostatic water, with some vendor sources extending to 35–40 days. Never freeze a reconstituted vial. This is a vendor-derived convention rather than a peptide-specific stability study — the window traces to the 0.9% benzyl alcohol preservative's antimicrobial validation, not to a Melanotan II-specific assay. See the Storage & handling primer for context.

For general storage chemistry (bacteriostatic vs sterile water, freeze-thaw, BUD framework), see Storage & handling.

Last reviewed: July 1, 2026

No controlled human studies have examined MT-II in combination with other agents. The following are reported in community settings only and are not supported by clinical trial evidence.

• UV tanning: MT-II is commonly paired with tanning-bed or natural sun exposure, with the rationale that MC1R stimulation and UV-induced melanocyte activation may additively enhance pigmentation. This practice has not been studied in controlled trials and may compound mutagenic stress on melanocytes. This use is anecdotal.

• PT-141 (bremelanotide): PT-141 is a direct metabolite of MT-II that acts selectively at MC3R and MC4R and is FDA-approved (Vyleesi, 2019) for hypoactive sexual desire disorder in premenopausal women. Community users report stacking MT-II with PT-141 to combine tanning with sexual-function effects. Overlapping receptor targets suggest additive nausea, flushing, and cardiovascular effects. This combination is entirely anecdotal and carries compounded, poorly characterised risks.

All combination use of MT-II is anecdotal and unsupported by clinical evidence.

Melanotan II is not currently FDA-approved for any indication. Effective April 22, 2026, the FDA removed Melanotan II from Category 2 of its Section 503A bulk drug substances list after the original nominators withdrew their nominations. This removal lifts the prior “significant safety risk” designation but does not place Melanotan II on the 503A Bulks List. Compounding pharmacies may prepare it with a valid physician prescription and pharmaceutical-grade API from an FDA-registered manufacturer. The FDA’s Pharmacy Compounding Advisory Committee (PCAC) is scheduled to review this substance at its July 23–24, 2026 public meeting. Removed from FDA Category 2 effective April 22, 2026. NOT selected for July 23-24, 2026 PCAC meeting. Deferred to second PCAC meeting before February 2027. NOT currently on 503A Bulks List — requires physician Rx. Source: FDA Advisory Committee Calendar / Lengea Law, May 2026.

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Reported side effects: Nausea, facial flushing, darkening of moles, potential cardiovascular effects

Adverse effects documented in controlled trials and published case reports include:

• Acute, dose-dependent: nausea (severe in 4 of 19 active injections in one double-blind RCT), facial flushing, spontaneous penile erections in males (1-5 hours post-dose), stretching and yawning, appetite suppression, and somnolence at higher doses.

• Dermatological: darkening of existing moles and eruptive formation of new dysplastic melanocytic nevi have been described in case reports (Hueso-Gabriel et al., Actas Dermosifiliogr 2012, PMID 22425244). At least four published cases describe melanoma arising during or shortly after MT-II use (including Ong and Bowling, Australasian J Dermatol 2012, PMID 22724573); direct causality is difficult to confirm given concurrent UV exposure in most reported cases. Melanonychia (brown-black nail discolouration) has also been described.

• Rare serious events (case reports only; true incidence unknown because no Phase III safety trial was completed): rhabdomyolysis, posterior reversible encephalopathy syndrome, renal infarction.

Use during pregnancy or breastfeeding is unsupported by any evidence and is advised against. Individuals with personal or family history of melanoma, numerous atypical nevi, or hereditary melanoma predisposition syndromes (such as FAMMM) carry substantially elevated theoretical risk. No formal drug-interaction data exist. Internet-sourced or compounded preparations carry additional contamination and sterility risks. MT-II is not approved by the FDA, EMA, MHRA, or TGA for any indication, and health authorities in the US, UK, and Australia have issued public safety warnings against its use.