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

Abstract

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.

Hydro-ethanolic leaf extract of Ziziphus abyssinica Hochst Ex A. Rich (Rhamnaceae) exhibits anti-nociceptive effects in murine models

“…Substances showing significant analgesic activity in tail-immersion test implicate both spinal and supra-spinal analgesic pathways as this test was developed to detect such compounds [ 50 , 51 ]. Aside the peripheral mechanisms involving the inhibition of the release of prostaglandins, leukotrienes, bradykinins and other endogenous substances, nociception can be modulated centrally through complex processes involving the opioidergic, serotoninergic, dopaminergic and adrenergic mechanisms [ 52 – 55 ]. Pain threshold in the test was significantly increased by EthE and this suggests that it may be acting spinally or supra spinally to interfere with the nociception process.…”