Department of Pharmacology,
University of Arizona College of
Medicine
Tucson, USA
PURPOSE: We evaluated the erectogenic
properties of a new cyclic
alpha-melanocyte-stimulating hormone analogue,
Melanotan-II, to treat men with psychogenic
erectile dysfunction.
MATERIALS AND METHODS: Ten men with erectile
dysfunction of no known organic cause were
entered in a double-blind, placebo controlled
crossover study in which the erectogenic
properties of Melanotan-II and a vehicle placebo
were compared using real-time RigiScan
monitoring. The presence, duration and rigidity
of erections were recorded during a 6-hour
period. RESULTS: In 8 of 10 men treated with
Melanotan-II clinically apparent erections
developed. Mean duration of tip rigidity greater
than 80% was 38.0 minutes with Melanotan-II and
3.0 with placebo (p=0.0045). Transient side
effects of nausea, stretching and yawning, and
decreased appetite were reported more frequently
after injections of Melanotan-II than placebo
but none required treatment.
CONCLUSIONS: Melanotan-II is a potent
initiator of erections in men with psychogenic
erectile dysfunction and has manageable side
effects at a dose of 0.025 mg./kg.
Episodes of penile erection, and the
stretching and yawning syndrome can be
induced in experimental animals by central
nervous system administration of
adrenocorticotropin and a-melanocyte-stimulating
hormone (a-MSH)? Central dopaminergic and
oxytocinergic receptors seem to mediate penile
erection and yawning but the effects of
adrenocorticotropin and a-MSH persist, despite
administration of j antagonists to oxytocin and
dopamine. This finding suggests that
melanotropic peptides act downstream to the
actions of dopamine and oxytocin.2
Melanotropin analogues have been developed
to promote skin pigmentation. Melanotan-II, a
superpotent cyclic melanotropic heptapeptide,
caused penile erections in a pilot phase 1
clinical trial when administered subcutaneously
to 3 normal men. We report the erectogenic
properties and side effect profile of
Melanotan-II in a double-blind, placebo
controlled crossover study of 10 men with
psychogenic erectile dysfunction.
...........
The side effects of nausea, stretching and
yawning, and decreased appetite were more
frequently reported after treatment with
Melanotan-II than placebo. Men who reported
moderate to severe nausea had received higher
dosages of Melanotan-II than the less
symptomatic group. At our preferred dose of
0.025 mg./kg. no subject reported moderate or
severe adverse reaction. We believe that the
stretching and yawning syndrome, noted in other
species, occurs in humans in response to
Melanotan-I1 but whether this is a direct effect
of the peptide or a response to somnolence is
unclear. Of note, the 2 patients who did not
have erections did not report yawning or nausea.
Finally, only 1 subject reported tanning but we
did not perform photometric testing to confirm
this finding nor did we control for sun exposure
during the experimental period. In previous
studies a cumulative dose of 0.1 mg./kg.
Melanotan-II was required for an increase in
skin pigmentation.5 Consideration of possible
clinical applications of this new peptide is
premature.
Further studies in a population with organic
erectile dysfunction may define appropriate
candidates for the use of Melanotan-II. The time
to onset of erection in our study is long for a
clinically useful drug but these patients were
not exposed to erotic stimuli and use of the
drug at home with sexual stimulation should lead
to a more rapid response. We believe that nasal
insufflation or other delivery systems may
provide more rapid absorption and be more
acceptable than subcutaneous injection of the
drug.
