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Abstract

Antinociceptive actions of BW373U86 in the mouse.

K D Wild, J McCormick, E J Bilsky, T Vanderah, R W McNutt, K J Chang and F Porreca
Journal of Pharmacology and Experimental Therapeutics November 1993, 267 (2) 858-865;
K D Wild
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J McCormick
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E J Bilsky
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T Vanderah
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R W McNutt
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K J Chang
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F Porreca
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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)

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Journal of Pharmacology and Experimental Therapeutics
Vol. 267, Issue 2
1 Nov 1993
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Abstract

Antinociceptive actions of BW373U86 in the mouse.

K D Wild, J McCormick, E J Bilsky, T Vanderah, R W McNutt, K J Chang and F Porreca
Journal of Pharmacology and Experimental Therapeutics November 1, 1993, 267 (2) 858-865;

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Abstract

Antinociceptive actions of BW373U86 in the mouse.

K D Wild, J McCormick, E J Bilsky, T Vanderah, R W McNutt, K J Chang and F Porreca
Journal of Pharmacology and Experimental Therapeutics November 1, 1993, 267 (2) 858-865;
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