Muscarinic receptor-mediated regulation of OM-853-enhanced dopamine release in striatum of rat.

The effect of OM-853, a new vincamine analogue, on cerebral dopaminergic neurons was investigated in male Wistar rats. The administration of OM-853 (200 mg/kg p.o.) induced facilitation of the metabolic turnover of dopamine (DA) in all brain areas except the cerebral cortex. Addition of OM-853 enhanced the release of [3H]DA from striatal slices; this release was antagonized by atropine (10(-7) M). However, pretreatment with scopolamine (0.5 mg/kg s.c.) inhibited the enhancement of striatal DA turnover induced by OM-853 administration. OM-853 (10(-4) M) inhibited [3H]quinuclidinyl benzilate binding to muscarinic cholinergic receptors in a striatal particulate fraction more potently than carbachol (10(-4) M). These results suggest that OM-853 may induce facilitation of striatal DA turnover by enhancing DA release via the stimulation of muscarinic cholinergic receptor.