The antimyoclonic action of clonazepam through a GABA--independent mechanism.
The present study investigates whether clonazepam exerts its antimyoclonic action through a GABA independent mechanism. We have studied the antimyoclonic effect of clonazepam and compared it with that of aminooxyacetic acid (AOAA), a GABA transaminase inhibitor, against myoclonus induced by picrotoxin, a GABA receptor antagonist and allylglycine, a drug which inhibits synthesis and release of GABA. We have also investigated the effect of clonazepam against picrotoxin-induced myoclonus in rats pretreated with either AOAA or submyoclonic dose of allylgylycine. Clonazepam pretreatment inhibited both picrotoxin and allylglycine-induced myoelonus whereas AOAA was effective in inhibiting only picrotoxin-induced myoclonus. The protective effect of clonazepam against picrotoxin-induced myoclonus was potentiated by AOAA pretreatment. Moreover, clonazepam afforded protection against picrotoxin-induced myoclonus in rats pretreated with a submyoclonic GABA reducing dose of allylglycine. These findings indicate that a GABA independent mechanism may also be involved in the antimyoclonic action of clonazepam.
Paul
V
V
Department of Pharmacology and Environmental Toxicology, University of Madras, Teramaui.
Krishnamoorthy
M S
MS
D000612:4-Aminobutyrate Transaminase / Q000378:metabolism; D000501:Allylglycine; D000625:Aminooxyacetic Acid; D000818:Animals; D000927:Anticonvulsants; D001923:Brain Chemistry / Q000187:drug effects; D002998:Clonazepam / Q000494:pharmacology*; D008297:Male; D009207:Myoclonus / Q000139:chemically induced / Q000188:drug therapy*; D010852:Picrotoxin; D051381:Rats; D011919:Rats, Inbred Strains; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000502:physiology*
D000612:4-Aminobutyrate Transaminase; D000501:Allylglycine; D000625:Aminooxyacetic Acid; D000927:Anticonvulsants; D002998:Clonazepam; D010852:Picrotoxin; D005680:gamma-Aminobutyric Acid