Participation of opioid mechanism in the antinociceptive effects induced by oxaprotiline enantiomers in mice.
The purpose of the present study was to assess the activity of (+)-oxaprotiline [(+)-OXA] (a noradrenaline uptake inhibitor) and (-)-oxaprotiline [(-)-OXA] (with unknown mechanism of action) in two experimental models of pain in mice, a hot plate test and a writhing syndrome induced by phenylbenzoquinone (PHBQ), and to determine whether the opioidergic system may be engaged in their antinociceptive effects. Morphine was used as a reference drug. Administration of (+)-OXA (0.31-5 mg/kg) and (-)-OXA (20 mg/kg) produced a statistically significant elevation of the nociceptive threshold, measured by the increased latencies in the hot plate test. Moreover, (+)-OXA (0.62-5 mg/kg) and (-)-enantiomer (5-20 mg/kg) decreased the number of writhing episodes induced by PHBQ in mice, (+)-enantiomer being more effective than (-)-OXA in either test. In the hot plate test, the analgesic effect induced by (+)-OXA (0.31 mg/kg) or (-)-OXA (20 mg/kg) was abolished by naloxone (2 mg/kg), an opioid receptor antagonist. In the writhing test, naloxone (2 mg/kg) partially, but not significantly, reduced the antinociceptive responses induced by (+)-OXA (0.62 mg/kg) or (-)-OXA (5 mg/kg). The obtained results show that both OXA enantiomers produce antinociception in mice which can be, at least partially, connected with opioid system.
Wesołowska
A
A
Department of New Drug Research, Institute of Pharmacology, Polish Academy of Sciences, Kraków.
Borycz
J
J
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D016227:Benzoquinones / Q000494:pharmacology; D004195:Disease Models, Animal; D008297:Male; D008376:Maprotiline / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D013237:Stereoisomerism
D000928:Antidepressive Agents; D016227:Benzoquinones; D009292:Narcotic Antagonists; D008376:Maprotiline; C029322:phenylbenzoquinone; D009270:Naloxone; C027299:hydroxymaprotilin