Melanotan II

Also known as: MT-II, MT2, Melanotan 2

Evidence: Clinical

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Overview

Synthetic cyclic alpha-MSH(4-10) analog that binds MC1, MC3, MC4 and MC5 receptors; small 1990s human trials found skin darkening and erections. Never approved.

Melanotan II (MT-II) was made at the University of Arizona as a lactam-bridged, enzyme-resistant fragment of alpha-MSH. A 1996 pilot in 3 healthy men produced tanning plus spontaneous erections, nausea and yawning, which led to two small placebo-controlled crossover trials in erectile dysfunction (n=10 each). Development moved to the close derivative bremelanotide (PT-141, a separate catalog entry), and MT-II was never approved anywhere. Product sold online for tanning is unlicensed, and case reports describe melanoma, rhabdomyolysis, priapism and renal infarction after use. Listed on FDA's 503A category 2 (safety concerns) page, withdrawn-nomination table, as of 2026-04-22: https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks

Benefits

Skin tanning (pilot human study, n=3), erections in men with erectile dysfunction (2 crossover RCTs, n=10 each), increased sexual desire (1 RCT, n=10), reduced food intake (mouse, central dosing)

Dosing reference

Research dose: 250 to 500 mcg daily loading: community range, no published protocol. Human trials used 0.01 to 0.03 mg/kg SC (weight-based)
Range: 250 to 500 mcg, 1x daily (loading)
Reconstitution: 2 mL bacteriostatic water
Common vial sizes: 10 mg

Human trials used weight-based subcutaneous doses: 0.01 to 0.03 mg/kg on alternate weekdays for 2 weeks in the pilot (0.025 mg/kg was recommended for further study), and single 0.025 mg/kg doses in the erectile dysfunction trials. The loading then 1 to 2x weekly maintenance pattern is community practice with no published protocol. Nausea, yawning, flushing and spontaneous erections were common after first doses in the trials.

Mechanism

Cyclic lactam analog of alpha-MSH(4-10) with Nle4 and D-Phe7 substitutions. Binding studies on cells expressing human receptors show high affinity at MC1, MC3, MC4 and MC5 receptors. MC1R activation on melanocytes is the proposed route to more eumelanin, consistent with the tanning seen in humans (Dorr et al., 1996). Central MC3/MC4 agonism suppresses feeding: intracerebroventricular MT-II inhibited food intake in four mouse models of hyperphagia, and the antagonist SHU9119 blocked the effect (Fan et al., 1997). In rats, MT-II induced erections through brain and spinal melanocortin receptors, the proposed basis of the erections in the human trials.

Evidence

Clinical: at least one published human trial or an approved drug

Pilot phase 1 in 3 healthy men: SC 0.01 to 0.03 mg/kg on alternate weekdays for 2 weeks increased facial and upper-body pigmentation; nausea, yawning and spontaneous erections were common (Dorr et al., 1996)
Double-blind crossover in 10 men with psychogenic erectile dysfunction: 0.025 mg/kg SC produced erections in 8 of 10, with tip rigidity over 80% lasting 38.0 vs 3.0 min on placebo (Wessells et al., 1998)
Crossover in 10 men with organic erectile dysfunction: erections after 12 of 19 MT-II injections vs 1 of 21 placebo, higher sexual desire, severe nausea after 4 of 19 injections (Wessells et al., 2000)
Intracerebroventricular MT-II inhibited feeding in four mouse models of hyperphagia, blocked by the antagonist SHU9119 (Fan et al., 1997)
Case reports after unlicensed use: melanoma (Hjuler and Lorentzen, 2014), sympathomimetic toxicity with rhabdomyolysis (Nelson et al., 2012), ischemic priapism (Mallory et al., 2021), renal infarction (Peters et al., 2020)
Human-trial status: never approved, and no trial since the small 1990s studies has published results. The derivative bremelanotide was approved by FDA in 2019 (Vyleesi, NDA 210557). Registered vitiligo record NCT07437560 calls itself an example record and is not evidence

References

Side effects

In the 1990s trials (n=3 and two of n=10), nausea, stretching and yawning, reduced appetite and spontaneous erections were common; 0.03 mg/kg caused grade II somnolence and fatigue in one subject, and 4 of 19 injections caused severe nausea (Wessells et al., 2000). Case reports after unlicensed use: melanoma in a 20-year-old after a 3 to 4 week course with sunbed use (Hjuler and Lorentzen, 2014); sympathomimetic toxicity, rhabdomyolysis (CK 17,773 IU/L) and renal dysfunction after a 6 mg injection (Nelson et al., 2012); acute ischemic priapism needing surgical decompression (Mallory et al., 2021); renal infarction (Peters et al., 2020); posterior reversible encephalopathy syndrome. FDA's category 2 entry cites possible immunogenicity and these case reports. Commonly reported (anecdotal): facial flushing, darkening of existing moles and new moles.

Storage

Storage: Refrigerated (2-8°C)
Lyophilized: 24+ months at room temperature
Reconstituted: 28-30 days refrigerated

Pharmacology

Half-life: No published human value. Rat IV (0.3 mg/kg): biphasic disposition; the beta half-life differed between HPLC and bioassay methods
Bioavailability: Subcutaneous: not measured in humans. Oral: 4.6% reported in rats in a 1994 preformulation study
Molecular weight: 1024.18 Da
Sequence: [Ac-Nle]DH[D-F]RWK[NH2] [lactam bridge between Asp and Lys side chains]