Effect of buflomedil (4-(1-pyrrolidinyl)-1-(2,4,6-trimethoxy phenyl)-1-butanone hydrochloride) on the function of striatal dopaminergic neurons.

Effect of buflomedil (4-(1-pyrrolidinyl)-1-(2,4,6-trimethoxy phenyl)-1-butanone hydrochloride) on the release and uptake of dopamine (DA) and the function of DA receptors in the striatum was investigated using male Wistar rats. In vitro addition of buflomedil (10(-5)-10(-8) M) had no effect on the uptake of [3H]-DA in striatal slices. On the other hand, buflomedil (10(-5)-10(-7) M) increased the spontaneous as well as high K+ (30 mM)-evoked releases of [3H]DA from striatal slices. Buflomedil inhibited the bindings of [3H]SCH23390, [3H]spiperone and [3H]apomorphine to striatal D1, D2 and D3 receptors only at a high concentration. On the other hand, buflomedil inhibited [3H]quinuclidinyl benzilate (QNB) binding to striatal muscarinic cholinergic receptors, which was similar to the action of carbachol. Pretreatment with scopolamine (0.5 mg/kg) in vivo inhibited the facilitation of striatal DA turnover induced by oral administration of buflomedil (300 mg/kg). In contrast, continuous oral administration of buflomedil (30 mg/kg x 7 days) to rats had no significant effect on the specific bindings of [3H]SCH23390, [3H]spiperone, [3H]apomorphine and [3H]QNB to synaptic membrane preparations obtained from the striatum. These results suggest that buflomedil may enhance striatal DA release by stimulating muscarinic cholinergic receptor and that DA receptors may not be involved in the enhancing effect of buflomedil on DA release.