# Melanotan 1 vs Melanotan 2 - Canonical: https://residue.info/vs/afamelanotide-vs-melanotan-ii/ - Compounds: Afamelanotide (https://residue.info/c/afamelanotide/), Melanotan II (https://residue.info/c/melanotan-ii/) - Updated: 2026-10-19 · Reviewed by: Residue Editorial Team Both are synthetic α-MSH analogs, but only one became a medicine. Afamelanotide (Melanotan I) is a melanocortin-1 receptor agonist approved as the Scenesse implant for erythropoietic protoporphyria [1][2]. Melanotan II is a shorter cyclic analog that also caused erections in small 1990s studies and was never approved [3][4]; FDA records case reports of melanoma [5]. ## Side by side | | Afamelanotide | Melanotan II | |---|---|---| | Structure | 13-residue α-MSH analog [6] | Cyclic, lactam-bridged α-MSH(4-10) analog [3] | | Receptor profile | Melanocortin-1 receptor agonist [1] | Non-selective melanocortin-receptor agonist [7] | | Effects in humans | Pigmentation; light tolerance in EPP [8][9] | Pigmentation, erections, nausea, yawning [3][4] | | Largest trial | Two RCTs, 168 patients with EPP [9] | 10-man placebo-controlled crossover studies [4][10] | | How it is given | 16 mg SC implant every 60 days in trials [9] | SC injection, 0.025 mg/kg in trials [4] | | Reported harms | Headache, nausea, implant-site reactions [1][11] | Case reports: melanoma, rhabdomyolysis, priapism [12][13][14] | | FDA | Approved: Scenesse, 2019 [2] | Not approved; withdrawn compounding nomination [5] | | Evidence grade | A | C | ## How are they related? Both mimic α-melanocyte-stimulating hormone. Afamelanotide was the first α-MSH analog given to people, chosen for higher activity and stability than the natural hormone [8]. Melanotan II, Ac-Nle4-Asp5-His6-D-Phe7-Arg8-Trp9-Lys10 α-MSH(4-10)-NH2, is a shorter, ring-closed version with superpotent melanotropic activity in vitro [3]. ## What is the evidence for afamelanotide? Two randomized, double-blind, placebo-controlled trials in erythropoietic protoporphyria (74 and 94 patients) found that a 16 mg implant every 60 days increased pain-free time in direct sunlight and improved quality of life [9]. It is approved in the US as Scenesse [2]. ## What is the evidence for Melanotan II? A three-man pilot in 1996 showed tanning after five low doses and spontaneous erections [3]. Two ten-man crossover studies then showed it initiated erections in men with psychogenic or organic erectile dysfunction [4][10]. Since then the literature is mainly case reports of harm after unsupervised use [12][13][7][14]. ## How should this evidence be read? The two compounds are not interchangeable. Afamelanotide's grade A applies only to its approved use in EPP; its tanning effect in volunteers is a separate, smaller body of evidence [8]. Melanotan II has no approval for any use, and products sold under either name online are not the approved drug [15]. ## Frequently asked questions **What is the difference between Melanotan 1 and Melanotan 2?** Melanotan I (afamelanotide) is selective for the melanocortin-1 receptor and approved for EPP [1][2]. Melanotan II is non-selective, also produces erections, and is not approved [7][4]. **Which is safer, Melanotan 1 or Melanotan 2?** Only afamelanotide has a regulated product and long-term safety follow-up, with mostly mild adverse events [8][1]. Melanotan II's safety data are a few small studies plus case reports of serious harm [12][13]. A 2017 review warns that unregulated melanotan I and II products both carry risks, including changes in moles [15]. **Are melanotan tanning injections legal?** Afamelanotide is approved only as Scenesse for EPP [2]. Products sold as melanotan for tanning are unregulated, and several national health bodies have issued warnings [15]. Rules vary by country; this is not legal advice. ## Sources [1] Afamelanotide: A Review in Erythropoietic Protoporphyria. Kim ES & Garnock-Jones KP Am J Clin Dermatol. 2016. https://pubmed.ncbi.nlm.nih.gov/26979527/ [2] Drugs@FDA: SCENESSE (NDA210797). CLIVUNEL INC; original approval 2019-10-08; Prescription. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=210797 [3] Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Dorr RT et al. Life Sci. 1996. https://pubmed.ncbi.nlm.nih.gov/8637402/ [4] Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study. Wessells H et al. J Urol. 1998. https://pubmed.ncbi.nlm.nih.gov/9679884/ [5] Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. U.S. FDA, content current as of 04/22/2026. https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks [6] PubChem compound record: Afamelanotide. C78H111N21O19 · MW 1646.8 g/mol. https://pubchem.ncbi.nlm.nih.gov/compound/16197727 [7] Melanotan II: a possible cause of renal infarction: review of the literature and case report. Peters B et al. CEN Case Rep. 2020. https://pubmed.ncbi.nlm.nih.gov/31953620/ [8] Pharmacokinetics and Pharmacodynamics of Afamelanotide and its Clinical Use in Treating Dermatologic Disorders. Minder EI et al. Clin Pharmacokinet. 2017. https://pubmed.ncbi.nlm.nih.gov/28063031/ [9] Afamelanotide for Erythropoietic Protoporphyria. Langendonk JG et al. N Engl J Med. 2015. https://pubmed.ncbi.nlm.nih.gov/26132941/ [10] Effect of an alpha-melanocyte stimulating hormone analog on penile erection and sexual desire in men with organic erectile dysfunction. Wessells H et al. Urology. 2000. https://pubmed.ncbi.nlm.nih.gov/11018622/ [11] Afamelanotide for prevention of phototoxicity in erythropoietic protoporphyria. Wensink D et al. Expert Rev Clin Pharmacol. 2021. https://pubmed.ncbi.nlm.nih.gov/33507118/ [12] Melanoma associated with the use of melanotan-II. Hjuler KF & Lorentzen HF Dermatology. 2014. https://pubmed.ncbi.nlm.nih.gov/24355990/ [13] Melanotan II injection resulting in systemic toxicity and rhabdomyolysis. Nelson ME et al. Clin Toxicol (Phila). 2012. https://pubmed.ncbi.nlm.nih.gov/23121206/ [14] Melanotan Tanning Injection: A Rare Cause of Priapism. Mallory CW et al. Sex Med. 2021. https://pubmed.ncbi.nlm.nih.gov/33460908/ [15] Risks of unregulated use of alpha-melanocyte-stimulating hormone analogues: a review. Habbema L et al. Int J Dermatol. 2017. https://pubmed.ncbi.nlm.nih.gov/28266027/ --- From Residue. Research and education only; not medical advice. Quote with attribution and a link to the canonical page.