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Differential effects of petit mal anticonvulsants and convulsants on thalamic neurones: GABA current blockade
Author(s) -
Coulter Douglas A.,
Huguenard John R.,
Prince David A.
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb14096.x
Subject(s) - picrotoxin , bicuculline , convulsants , pentylenetetrazol , chemistry , gaba receptor antagonist , anticonvulsant , strychnine , pharmacology , nipecotic acid , neuroscience , gabaa receptor , epilepsy , neurotransmitter , medicine , receptor , biochemistry , biology
1 Currents evoked by applications of γ‐aminobutyric acid (GABA) to acutely dissociated thalamic neurones were analysed by voltage‐clamp techniques, and the effects of the anticonvulsant succinimides ethosuximide (ES) and α‐methyl‐α‐phenylsuccinimide (MPS) and the convulsants tetramethylsuccinimide (TMS), picrotoxin, pentylenetetrazol (PTZ), and bicuculline methiodide were assessed. 2 TMS (1 μ m ‐10 m m ) reduced responses to iontophoretically applied GABA, as did picrotoxin (0.1–100 μ m ), PTZ (1–100 m m ) and bicuculline (1–100 μ m ). 3 ES, in high concentrations (1–10 m m ), reduced GABA responses to a lesser extent, and also occluded the reductions in GABA‐evoked currents produced by TMS, picrotoxin, and PTZ. ES did not occlude the effects of bicuculline on GABA responses. Therefore, we propose that ES acts as a partial agonist at the picrotoxin GABA‐blocking receptor. 4 MPS had no effect on GABA responses (at a concentration of 1 m m ), and, like ES, occluded the GABA‐blocking actions of TMS, apparently acting as a full antagonist. 5 The anticonvulsant actions of ES and MPS against TMS and PTZ‐induced seizures may thus involve two independent mechanisms: (1) the occlusion of TMS and PTZ GABA‐blocking effects; and (2) the previously described specific effect of ES and MPS on low‐threshold calcium current of thalamic neurones. The latter cellular mechanism may be more closely related to petit mal anticonvulsant activity.