The involvement of central cholinergic system in (+)-matrine-induced antinociception in mice.

The antinociceptive effect of (+)-matrine was examined in mice by writhing, tail-pressure and hot-plate tests. (+)-Matrine (5, 10 and 20 mg/kg s.c.) produced antinociception in a dose-dependent manner. In hot-plate test, the antinociception produced by (+)-matrine (10 mg/kg s.c.) was attenuated by muscarinic receptor antagonists atropine (5 mg/kg i.p.) and pirenzepine (0.1 mug/mouse i.c.v.) and acetylcholine depletor hemicholinium-3 (HC-3) (1 mug/mouse i.c.v.), but not by opioid receptor antagonist naloxone (2 mg/kg i.p.), dopamine D(2) receptor agonist (-)-quinpirole (0.1 mg/kg i.p.) or catecholamine depletor reserpine (2.5 mg/kg i.p.). Radioligand binding assay demonstrated that (+)-matrine had no affinity for mu-, kappa- or delta-opioid receptors in a wide concentration range (1 x 10(-11)-1 x 10(-3) M). The results suggest that (+)-matrine exerts its antinociceptive effect through multiple mechanism(s) such as increasing cholinergic activation in the CNS rather than acting on opioid receptors directly.