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.
Youdim
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Ashkenazi
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D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D003010:Clorgyline / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008732:Methoxydimethyltryptamines / Q000494:pharmacology; D008995:Monoamine Oxidase / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014191:Tranylcypromine / Q000494:pharmacology; D014364:Tryptophan / Q000037:antagonists & inhibitors; D010133:p-Chloroamphetamine / Q000037:antagonists & inhibitors
D014151:Anti-Anxiety Agents; D002395:Catecholamines; D008732:Methoxydimethyltryptamines; D010880:Piperidines; D012702:Serotonin Antagonists; D012701:Serotonin; D014191:Tranylcypromine; D013792:Thalidomide; D010133:p-Chloroamphetamine; D014364:Tryptophan; D008995:Monoamine Oxidase; C027948:supidimide; D003010:Clorgyline; C018181:indalpine