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Stereospecific inhibition of oxotremorine-induced antinociception by (+) -isomers of opioid antagonists: comparison with opioid receptor agonists

Ben-Sreti, M.M.; Sewell, R.D.

Journal of Pharmacy and Pharmacology 34(8): 501-505

1982

ISSN/ISBN: 0022-3573
PMID: 6126560
DOI: 10.1111/j.2042-7158.1982.tb04773.x
Accession: 044399169
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The antagonistic effects of the two benzomorphan opioid antagonists, Mr-1452 and Mr-2266 and their respective (+)-isomers Mr-1453 and Mr-2267 upon morphine, ethylketocyclazocine (EKC), D-ala2-D-leu5-enkephalinamide (BW 180-C) and oxotremorine (OTMN) antinociceptive activity in mice were investigated. Pretreatment with either Mr-1452 (2.0 mg Kg-1 i.p.) or Mr-2266 (2.0 mg kg-1 i.p.) significantly antagonized the antinociceptive effects of the three opioid agonists in the hot plate test, but were ineffective against OTMN, which in contrast was antagonized by the (+)-isomers. Interaction between the antagonists and submaximal analgesic doses of the opioids or OTMN produced similar results in the tail immersion assay. However, the effect of Mr-2267 on OTMN was biphasic and this contrasted with Mr-1453 which produced consistent and graded antagonism.

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