Differential effects of petit mal anticonvulsants and convulsants on thalamic neurones: GABA current blockade

British Journal of Pharmacology
D A CoulterD A Prince

Abstract

1. Currents evoked by applications of gamma-aminobutyric acid (GABA) to acutely dissociated thalamic neurones were analysed by voltage-clamp techniques, and the effects of the anticonvulsant succinimides ethosuximide (ES) and alpha-methyl-alpha-phenylsuccinimide (MPS) and the convulsants tetramethylsuccinimide (TMS), picrotoxin, pentylenetetrazol (PTZ), and bicuculline methiodide were assessed. 2. TMS (1 microM-10 microM) reduced responses to iontophoretically applied GABA, as did picrotoxin (0.1-100 microM), PTZ (1-100 mM) and bicuculline (1-100 microM). 3. ES, in high concentrations (1-10 mM), 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 mM), 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 effe...Continue Reading

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Citations

Jun 1, 1994·Hippocampus·U HeinemannC Zhang
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Feb 13, 2014·Pflügers Archiv : European journal of physiology·Eunji Cheong, Hee-Sup Shin
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Sep 13, 2003·British Journal of Pharmacology·Slobodan M TodorovicVesna Jevtovic-Todorovic
Aug 1, 2013·Physiological Reviews·Eunji Cheong, Hee-Sup Shin

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