title: Antinociceptive actions of BW373U86 in the mouse.
abstract: This study explored the antinociceptive properties of (+-)-4-[(alpha- R*)-alpha-[(2S*,5R*)-4-allyl-2,5-dimethyl-1-piperazinol]-3-hydroxy benzyl] - 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 mumol/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 alpha-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.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology, University of Arizona Health Sciences Center, Tucson.
authors.forename: K D
authors.initials: KD
authors.lastname: Wild
authors.forename: J
authors.initials: J
authors.lastname: McCormick
authors.forename: E J
authors.initials: EJ
authors.lastname: Bilsky
authors.forename: T
authors.initials: T
authors.lastname: Vanderah
authors.forename: R W
authors.initials: RW
authors.lastname: McNutt
authors.forename: K J
authors.initials: KJ
authors.lastname: Chang
authors.forename: F
authors.initials: F
authors.lastname: Porreca
mesh_terms: D000005:Abdomen; D000085:Acetates; D019342:Acetic Acid; D000595:Amino Acid Sequence; D000818:Animals; D001549:Benzamides / Q000378:metabolism / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008566:Membranes / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D009619:Nociceptors / Q000187:drug effects*; D010147:Pain Measurement / Q000187:drug effects; D010879:Piperazines / Q000378:metabolism / Q000494:pharmacology*; D011869:Radioligand Assay; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D000085:Acetates; D001549:Benzamides; D010879:Piperazines; D011957:Receptors, Opioid; C083877:BW 373U86; D019342:Acetic Acid