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The Effect of Anticonvulsant Drugs on GABA-Stimulated Chloride Uptake

Published online by Cambridge University Press:  18 September 2015

J. Francis ,
S.J. Mihic ,
W.B. Sneddon  and
W.M. Burnham
J. Francis
Affiliation:
Department of Pharmacology, University of Toronto, Toronto Bloorview Epilepsy Program, University of Toronto, Toronto
S.J. Mihic
Affiliation:
Department of Pharmacology, University of Toronto, Toronto
W.B. Sneddon
Affiliation:
Department of Pharmacology, University of Toronto, Toronto
W.M. Burnham*
Affiliation:
Department of Pharmacology, University of Toronto, Toronto Bloorview Epilepsy Program, University of Toronto, Toronto
*
Department of Pharmacology, Medical Sciences Building, University of Toronto, Toronto, Ontario, Canada M5S 1A8
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Abstract:

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Eight anticonvulsant drugs – including clonazepam, diazepam and phenobarbital – were tested for their effects on GABA-stimulated chloride uptake in rat cerebral cortical microsacs (unfiltered synaptoneurosomes). “Mid” and “high” therapeutic concentrations were screened, and, if significant enhancement was found, full concentration-response tests were done. In the initial screens, enhancement of GABA-stimulated uptake was found only with phenobarbital, clonazepam and diazepam. In subsequent concentration-response tests, the effects of phenobarbital were found to occur throughout the range of normal, anticonvulsant concentrations, whereas the effects of clonazepam and diazepam were observed only above the concentrations normally used for the chronic control of seizures or anxiety. These data suggest that phenobarbital's anticonvulsant effects are mediated via the GABAA receptor complex, but that the low-dose effects of the benzodiazepines may be mediated via some other mechanism.

Type
Articles
Information
Canadian Journal of Neurological Sciences , Volume 21 , Issue 1 , February 1994 , pp. 3 - 8
Copyright
Copyright © Canadian Neurological Sciences Federation 1994

References

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