The effects of the long-acting opioid antagonist, nalmefene [17-N-cycloprop
ylmethyl-3,14-beta-dihydrox-4,5-alpha-epoxy-6-methylene morphinan hydrochlo
ride] on LH, T, and prolactin release in rhesus monkeys are unknown. The ac
ute effects of nalmefene (0.01 and 0.10 mg/kg, IV) or placebo on LH, PRL, a
nd T were studied, and samples were collected at 10-min intervals for 360 m
in to permit cluster analysis of pulsatile release patterns. LH increased s
ignificantly within 30 min after nalmefene, and remained significantly abov
e baseline levels for 50 to 60 min (p < 0.05). Testosterone increased signi
ficantly within 70 to 80 min after nalmefene, and remained significantly ab
ove baseline for 60 min (p < 0.05). Although nalmefene antagonizes opioid a
gonists for 6-8 h, inhibitory feedback by testosterone appeared to limit th
e duration of its antagonism of endogenous opioid inhibition of LHRH and st
imulation of LH. Nalmefene did not change LH or PRL pulse frequency or ampl
itude significantly in comparison to placebo administration. (C) 2000 Elsev
ier Science Inc.