EVALUATION OF MELANOTAN-II, A SUPERPOTENT CYCLIC MELANOTROPIC PEPTIDEIN A PILOT PHASE-I CLINICAL-STUDY

A pilot phase I study was conducted with a cyclic heptapeptide analog of cr-melanocyte stimulating hormone (a-MSH). The lactam-bridged molec ule, called Melanotan-II has the structure -D-Phe(7)-Arg(8)-Trp(9)-Lys (10)alpha-MSH(4-10)-NH2 (MT-II) and has superpotent melanotropic activ ity in vitro. A single-blind, alternating day (saline or MT-II), place bo-controlled trial was conducted in 3 normal male volunteers at the s tarting dose of 0.01 mg/kg of MT-II. Subcutaneous injections of MT-II or saline were given daily (Monday-Friday) for 2 consecutive weeks. Tw o subjects were escalated by 0.005 mg/kg increments to 0.03 mg/kg and one to 0.025 mg/kg. The 0.03 mg/kg dose produced Grade II somnolence a nd fatigue in one of two subjects (WHO standards). Mild nausea, not re quiring antiemetic treatment, was reported at most MT-II dose levels. A stretching and yawning complex appeared to correlate with the onset of spontaneous, penile erections which were intermittently experienced for 1-5 hours after MT-II dosing, depending on the MT-II dose. Two su bjects had increased pigmentation in the face, upper body and buttock, as measured by quatitative reflectance and by visual perception 1 wee k after MT-II dosing ended. These results demonstrate that MT-II has t anning activity in humans given only 5 low doses every other day by su bcutaneous injection. The recommended single MT-II dose for future Pha se I studies is 0.025 mg/kg/day.