Antimyoclonic action of clonazepam: the role of serotonin.
Clonazepam (5-(2-chlorophenyl)-1,3-dihydro-7-nitro 2H-1,4 benzodiazepin-2-one) (2 mg/kg) reduced a p,p'-DDT-induced myoclonus in mice by 50%. This antimyoclonic action of clonazepam was counteracted by the serotonin (5-HT) receptor blockers methysergide, metergoline and cinnanserin and potentiated by the 5-HT uptake inhibitors fluoxetine and chlorimipramine. Clonazepam (4 mg/kg) reduced plasma tryptophan by 27%, but had no effect on brain tryptopham, 5-HT, 5-hydroxyindoleacetic acid, 5-HT synthesis and 3H-5-HT receptor binding. Clonazepam (10(-5) M) inhibited brain synaptosomal 3H-5-HT uptake by 23% and increased 3H-5-HT release by 24%. However, 2-8 mg/kg of clonazepam administered intraperitoneally had no effect on 5-HT uptake or release. gamma-Aminobutyric acid (GABA) agonists (muscimol, acetylenic GABA, amino-oxyacetic acid) and the GABA antagonists bicuculline and isoniazid had no effect on p,p'-DDT-induced myoclonus. Furthermore, bicuculline did not counteract the antimyoclonic effect of clonazepam. We suggest that the antimyoclonic action of clonazepam is mediated by enhancement of serotonergic rather than GABAergic neurotransmission.
D000818:Animals; D000927:Anticonvulsants; D001570:Benzodiazepinones / Q000494:pharmacology*; D002998:Clonazepam / Q000494:pharmacology*; D003634:DDT / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D009207:Myoclonus / Q000139:chemically induced / Q000503:physiopathology*; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000502:physiology*; D013574:Synaptosomes / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism
D000927:Anticonvulsants; D001570:Benzodiazepinones; D011985:Receptors, Serotonin; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D002998:Clonazepam; D014364:Tryptophan; D003634:DDT