Action of S 1432, a new psychotropic drug, on the central cholinergic system

S 1432 (hydroxyethyl-9', purinyl-6'-1-benzhydryl-4-piperazine dihydrochloride), an anticonvulsant, muscle relaxant and CNS depressant in experimental animals, increased the acetylcholine level in the striatum (50%) hippocampus (25%) and mesencephalon (15%) but not in the diencephalon or hemispheric residuum of the rat at doses of 20 and 40 mg/kg, i.p. The effect lasted for about 120 min after a single dose of 40 mg/kg. The drug markedly decreased the choline level in the striatum but not in the other brain areas observed. The action of S 1432 on striatal acetylcholine was not blocked by pimozide indicating that the increase was not modulated through dopaminergic neurons. Furthermore, the drug did not alter whole brain or brain area levels or the turnover of noradrenaline, serotonin or dopamine although there was a tendency towards a decrease in the latter. Pretreatment with S 1432 prevented pentylenetetrazol convulsions in 11/12 rats. Under these conditions, pentylenetetrazol completely antagonized the effect of S 1432 on striatal but not hippocampal acetylcholine. Thus, similarly to diazepam (14), a biochemical interaction of S 1432 with pentylenetetrazol is demonstrated.