Serotonergic involvement in pharmacological action of the anxiolytic-sedatives thalidomide and supidimide

The anxiolytic-sedative drugs thalidomide and supidimide inhibited spontaneous motor activity in rats. Both compounds inhibited the serotonin (5-HT) behavioural syndrome induced by tranylcypromine (TCP) plus L-tryptophan (TRP) or clorgyline plus the selective 5-HT uptake blocker, LM 5008 (4-[2-(3-indolyl)ethyl]piperidine) and delayed the behavioural effects of p-chloro-amphetamine, a releaser of 5-HT. The behavioural syndrome induced by the 5-HT agonist, 5-methoxy-N,N'-dimethyltryptamine (5-MeODMT) was unaffected by supidimide pretreatment. Thus supidimide does not possess 5-HT receptor antagonistic properties. This was further substantiated by the unaltered 5-HT-induced platelet aggregation in the presence of supidimide (10(-7)-10(-4) M). A decrease of 5-HT release into the synaptic cleft will lead to a diminished behavioural response to drugs that act presynaptically. Supidimide induced a greater increase in accumulation of brain 5-HT in TCP (5 mg/kg) plus TRP (100 mg/kg)-treated animals as compared to that in the corresponding controls. These data indicate that the behavioural and pharmacological actions of supidimide may be related to its inhibition of 5-HT release.