Participation of opioid mechanism in the antinociceptive effects induced by oxaprotiline enantiomers in mice

Abstract

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.