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.