ICP #001: melanotan II
The inaugural Interesting Compound Profile
Something new – I’m trying out write-ups of interesting chemicals. Let me know what you think.
Melanotans are funny compounds. They bind to melanocortin receptors (MCRs), which is what lets them acts as “sunless tanning” drugs – they’re basically activating the same pathways triggered by exposure to UV light.
But there are lots of different melanocortin receptors; the tanning action (or ‘melanogenesis’) is specifically due to their activity at the MC1 receptor. They bind to other melanocortin receptor subtypes too, which gives them other effects – notably nausea and sexual arousal.
Which leads to amusing snippets from papers like this, where one of the compound’s inventors mistakenly tested a heroic dose on himself1:
Unlike MTI, however, MTII caused a rather immediate, unexpected response: nausea and, to my great surprise, an erection (no figure provided). While I lay in bed with an emesis pan close by, I had an unrelenting erection (about 8 h duration) which could not be subdued even with a cold pack. When my wife came upon the scene, she proclaimed that I “must be crazy.” In response, I raised my arm feebly into the air and answered, “I think we may become rich.”
Melanotan I, now known as afamelanotide, is approved for erythropoietic protoporphyria, a disorder involving a lack of skin pigment that causes sufferers to burn in the sun. Because it has such a short half-life, it has to be delivered as an implant under the skin.
Melanotan II has a much longer half-life, so it can be injected subcutaneously (which is probably cheaper than an implant, and preferable to the patient). It’s not clear why it never got approved for human use, but one explanation is that for a single compound, it does too many different things.
Palatin Technologies, the licence holder for MTII, created the MTII analogue bremelanotide, which treats sexual dysfunction without the tanning effects. Sexual dysfunction is much more common than erythropoietic protoporphyria and so more lucrative – it’s likely that putting MTII through clinical trials wasn’t commercially prudent, and so development was dropped.
Of course that doesn’t stop people getting hold of it through other means, and it’s easily available online. This especially fun paper sees two scientists talk to an exotic dancer in Ireland about her life and drug use.