ETORPHINES - MU-OPIOID RECEPTOR-SELECTIVE ANTINOCICEPTION AND LOW PHYSICAL-DEPENDENCE CAPACITY

Comparative analgesic studies revealed that dihydroetorphine was more potent than etorphine in the tail-flick and hot-plate tests, respectiv ely and nearly equipotent in the phenylquinone assay. Both compounds w ere short acting. Studies with selective opioid receptor antagonists b eta-funaltrexamine, nor-binaltorphimine and naltrindole revealed that both etorphines were mu-selective agonists. Presumptive evidence for c ompetitive antagonism of these compounds with naloxone was provided by Schild regressions with slopes of near unity. In a suppression test i n rhesus monkeys maximally dependent on morphine, dihydroetorphine and etorphine dose-dependently replaced morphine. Drug-naive simians chro nically exposed to frequent, intermittent and escalating doses of dihy droetorphine for 42 days showed few withdrawal signs when challenged w ith large doses of naloxone or were abruptly withdrawn from this drug. The results suggest that these atypical opioids may be useful in the clinical treatment of pain and opiate drug abuse. (C) 1997 Elsevier Sc ience B.V.