“Discovery That a Melanocortin Regulates Sexual Functions in Male and Female Humans”, 2005-10 (; backlinks):
Melanocortins (MCs) are multifunctional peptide hormones that regulate a diversity of physiological functions. MCs have been implicated in sexual function in animals.
We document here that a MC analog, Melanotan II (MTII), can enhance sexual function in human males (erectile activity) and females (increased levels of sexual desire and genital arousal). Unlike other sexual-enhancement drugs, MTII works at the level of the brain, thus eliciting a rather natural sexual response with minimal or no undesirable side effects.
The actions of the peptide were discovered accidentally while studying the effects of the peptide and related analogs on human skin pigmentation (tanning).
[Keywords: melanocortins, MTI & MTII, MSH]
…A role for a MC in human reproductive function provides an interesting story which emphasizes the old adage that “Chance favors the prepared mind”, or put another way, “Keep your eyes open in the laboratory for the unexpected.” In the present context, discovery was such an uplifting event that it could not have gone very easily without notice.
…During the development of MTI, I served as a proverbial “human pincushion” (a.k.a. guinea pig), that is, I tested the efficacy of the peptide to produce a tan on myself. Therein lies a very interesting story. Our group of University investigators (Hadley, Hruby and his student Fahad Al-Obeidi) prepared and characterized some fragment [Nle4, DPhe7]-substituted MC analogs that proved to be as potent as MTI, even though structurally only half the size (seven amino acids) of the parent analog1,2. In addition, the melanotropin, MTII, Ac-Nle-c[Asp, HisDPhe, Arg, Trp, Lys]-NH2, was conformationally restrained by a lactam bridge to provide a cyclic structure of increased lipophilicity (Figure 1). The smaller molecule is just as active as the larger MTI; it is cheaper to synthesize and might gain access more readily into the body. Based upon these and other considerations, a sterile preparation was provided for injection to determine its tanning potential.
One mistake in my deliberations was made, however. MTI had previously been administered at a dose as high as 10 mg without physiological consequences (other than tanning). I forgot, however, that MTII was only about half the molecular weight of MTI (Figure 1). Therefore, when I took an equivalent (10 mg) dose of MTII, I inadvertently received about twice the number of molecules of the peptide. 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 8h 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.”
Realizing the importance of the observation, I was determined to find out what a lower dose of MTII might do. So several days later, I used half (5 mg) of the previous dose. This again elicited an immediate erection which, however, only lasted about 5h with somewhat less nausea. Again, at a later date, I cut the dose in half (2.5 mg), and this resulted in an erection of only 2–3 h duration, with only minimal nausea. I now knew I was on the right track. So when I administered about half the previous dose (1.25 mg) there was no nausea and only a feeble wobble, a response which, however, could be rather easily coaxed to a full erectile response following a few erotic reflections. Further experimentation demonstrated that a dose of about 1.5–2.0 mg of MTII invariably induced a full erection without much conscious effort in myself and other volunteers. MTII was licensed to Palatin Technologies (Elizabeth, NJ;
Palatin@aol.com). To my knowledge, MTII (referred to by Palatin as “PT-141”, and by myself as “erectide”) has never failed to induce an erection in men with claimed impotence but known to be able to achieve an erection as proven by monitoring nocturnal penile tumescence (by a meter, a “peter meter”?). MTII, like other peptides, cannot as yet successfully be delivered by the alimentary (oral) route. MTII, however, is presently being effectively delivered as a nasal spray (“sniff a stiff”).…When I first discovered the dramatic erectile response to an overdose of MTII, I also noted (as I lay in bed) that I was constantly vigorously stretching and yawning (acting like a rat). We can conclude, therefore, that MTII, unlike MTI, is able to cross the blood-brain barrier to mediate its actions in the brain as a neurohormone.
…The above story, although initially based upon less scientific methodology than is usually undertaken in the conventional university research laboratory, has been further documented by hundreds of other individuals. The importance of the initial discovery (an erectile response) was immediately recognized for its importance as was also the earlier discovery of the unique action of MTI. As reported elsewhere7, injections of MTI into a golden retriever resulted in the growth of black hair in a previously all-yellow dog. The potential use of MTI as a possible tanning agent was obvious. Both these observations with MTI and MTII prove the old adage that, indeed, “Chance favors the prepared mind.”