A nonpeptidic delta opioid receptor agonist, BW373U86, attenuates the development and expression of morphine abstinence precipitated by naloxone in rat.
The effect of (+-)-4-((alpha-R*)-alpha-((2S*,5R*)-4-allyl-2,5-dimethyl-1- piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide (BW373U86), the first potent nonpeptidic, highly selective delta opioid receptor agonist, on morphine dependence was studied in rats. Continuous infusion of BW373U86 by a subcutaneously implanted osmotic minipump did not induce any abnormal behavior. After 6 days of BW373U86 infusion, intraperitoneal injection of a high dose of naloxone or naltrindole did not precipitate morphine-like abstinence syndromes. Furthermore, a single injection of BW373U86 did not induce abstinence syndromes or modulate morphine abstinence precipitated by naloxone in chronic morphine-treated rats. However, naloxone-precipitated abstinence syndromes in morphine-dependent rats were partially suppressed by BW373U86 in a dose-dependent manner when the compound was infused subcutaneously before and throughout morphine treatment. Abstinence signs such as wet-dog shake, forelimb tremor and teeth chattering were either suppressed or the intensity was significantly attenuated in these BW373U86-infused rats. This effect was antagonized by naltrindole. These data show that chronic infusion of BW373U86 does not produce physical dependence and that it attenuates some abstinence behaviors in morphine-dependent rats via delta opioid receptors.
Lee
P H
PH
Division of Cell Biology, Burroughs Wellcome Co., Research Triangle Park, North Carolina.
McNutt
R W
RW
Chang
K J
KJ
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D008297:Male; D009020:Morphine / Q000009:adverse effects*; D009021:Morphine Dependence / Q000503:physiopathology; D009270:Naloxone / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000187:drug effects / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D013997:Time Factors
D001549:Benzamides; D010879:Piperazines; D017465:Receptors, Opioid, delta; C083877:BW 373U86; D009270:Naloxone; D009020:Morphine