The antidopaminergic action of S-20098 is mediated by benzodiazepine/GABA(A) receptors in the striatum.
The naphthalenic compound S-20098, which is a melatonergic agonist, inhibits [3H]diazepam binding in striatal membranes. S-20098 also inhibits apomorphine-induced turning in 6-hydroxydopamine lesioned rats. This antidopaminergic effect is blocked by either intraperitoneal injection of the central-type benzodiazepine (BZ) antagonist, flumazenil, or intrastriatal injection of the GABA(A) antagonist, bicuculline. These findings indicate that S-20098 can activate central-type BZ receptors, and its antidopaminergic action, like that of melatonin, involves a GABAergic mechanism in the striatum.
Tenn
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Department of Biomedical Sciences, McMaster University, Hamilton, Ont., Canada.
Niles
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D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D005442:Flumazenil / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D007267:Injections; D007274:Injections, Intraperitoneal; D008297:Male; D008550:Melatonin / Q000819:agonists*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology*; D009281:Naphthalenes
D000081:Acetamides; D001640:Bicuculline; D018492:Dopamine Antagonists; D005442:Flumazenil; D018756:GABA Antagonists; D018757:GABA Modulators; D008550:Melatonin; D011963:Receptors, GABA-A; C084711:agomelatine; D009281:Naphthalenes