This study explored the antinociceptive properties of (±)-4-[(α-F*)- α-[(2S*,5R*)-4-allyl-2,5-dimethyl-1-piperazinol]-3-hydroxybenzyl]-N,N- diethyl-benzamide dihydrochloride (BW373U86) a nonpeptidic compound proposed to be a delta opioid agonist, using three models of nociception and four routes of administration in mice. BW373U86 produced dose- and time-dependent, naloxone-sensitive antinociception in both the tail-flick and tail-pinch assays when given intrathecally (i.t.). However, at doses up to 187 nmol/mouse, i.c.v. BW373U86 was inactive in the tail-flick or tail-pinch assays. Additionally, at doses up to 187 μmol/kg, BW373U86 was not active after i.p. or p.o. administration in these endpoints. Further, in the tail- flick test, i.c.v. BW373U86 did not antagonize the antinociceptive effects of i.c.v. [D-Pen2,D-Pen5]enkephalin or [D-Ala2,Glu4]deltorphin, but partially antagonized the effects of i.c.v. morphine. In the acetic-acid abdominal constriction assay. BW373U86 produced dose-dependent antinociceptive effects when given by the i.p., i.c.v. or i.t., but not by the p.o., routes. Intrathecal BW373U86 was 663-fold more potent in the abdominal constriction assay than when given by the same route in the tail- flick test. The effects of an A70 dose of i.p. or i.c.v. BW373U86 in the abdominal constriction assay were partially antagonized by i.c.v. naloxone, but not by i.c.v. N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH, where Aib is α- aminoisobutyric acid (ICI-174,864) or naltrindole. In contrast, i.t. naloxone. ICI-174,864 or naltrindole antagonized the antinociceptive effect of i.p. or i.t. BW373U86 in the abdominal constriction assay. These data suggest that BW373U86 can be classified as a partial opioid agonist with actions at delta as well as mu receptors. The actions of lower doses of BW373U86 at spinal levels appears to involve a delta mechanism whereas supraspinal effects appear to be associated with interactions at mu sites.
|Original language||English (US)|
|Number of pages||8|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - Jan 1 1993|
ASJC Scopus subject areas
- Molecular Medicine