Effects of clozapine in a selective muscarinic bioassay and on single cells of the rat hippocampus.

Acetylcholine was applied to isolated crayfish hindguts and caused dose-dependent increases in its contractile force. These effects were blocked by muscarinic but not by nicotinic antagonists. Dopamine, noradrenaline, enkephalin or GABA agonists had either no effect or one distinct from the action of acetylcholine. Of a number of antischizophrenic drugs, clozapine had the strongest antimuscarinic action with a pA 2 value of 7.5, followed by thioridazine with a pA 2 value of 6.7. All other drugs of the phenothiazine, butyrophenone or benzamide type were ineffective. From these results, it was concluded that the crayfish hindgut is a very reliable and simple bioassay for muscarinic actions of drugs. Clozapine was also applied by microiontophoresis to cat hippocampal neurons and its effects on carbachol-, acetylcholine- and glutamate-induced excitations was assessed. It displayed an inhibitory action on excitations induced by the cholinergic agents, but did not visibly affect those induced by glutamate. The fact that clozapine had strong antimuscarinic effects on the crayfish hindgut as well as on hippocampal neurons of a mammalian indicates a similarity between the muscarinic receptors in both tissues.