Premium
Anticonvulsant Activity of Muscimol and γ‐Aminobutyric Acid Against Pyridoxal Phosphate‐Induced Epileptic Seizures
Author(s) -
Kouyoumdjian Jean Claude,
Ebadi Manuchair
Publication year - 1981
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1981.tb02401.x
Subject(s) - muscimol , aminooxyacetic acid , convulsion , diazepam , gabaa receptor , vigabatrin , anticonvulsant , chemistry , gaba transaminase , pyridoxal phosphate , medicine , glutamate decarboxylase , endocrinology , gaba receptor antagonist , biochemistry , bicuculline , epilepsy , pharmacology , biology , receptor , enzyme , cofactor , neuroscience
The intracerebroventricular injection of pyridoxal phosphate (PLP, 0.125‐1.25 μmol/rat) causes epileptic seizures (4 min → 1 min) that are preventable or reversible by GABA (1 μmol/rat), by muscimol (O.025 μmol/rat), or by diazepam (1.75 μmol/rat). At the peak of PLP‐induced convulsions, the activities of GAD and GABA‐T in 14 regions of rat brain remained unaltered, whereas the concentrations of PLP remained elevated. The PLP‐induced convulsion was blocked by DABA (10 μmol/rat) but was not altered by β‐alanine (50 μmol/rat). The previous in vitro studies have shown that PLP increases the uptake of [ 3 H]GABA into synaptosomes and inhibits the binding of [ 3 H]GABA to synaptic membranes. These data suggest that PLP‐induced convulsion is due to reduced availability of GABA to its recognition sites, rather than to alteration in the activity of GABA metabolizing enzymes, or unavailability of PLP as a coenzyme for GAD and GABA‐T. Since the duration of PLP‐induced epileptic seizures is short and can be prevented by GABA agonists, PLP may be used as a tool to study the nature of GABA‐mediated neuroinhibition and the properties of GABA receptor sites.