Inhibitory effects of anticonvulsant drugs on cyclic nucleotide accumulation in brain

Annals of Neurology
J A Ferrendelli, D A Kinscherf

Abstract

Veratridine causes deplorization of excitable cells and produces marked elevation of adenosine 3',5'-monophosphate (cyclic AMP) and guanosine 3',5'-monophosphate (cyclic GMP) levels in incubated slices of mouse cerebral cortex. Phenytoin, carbamazepine, phenobarbital, primidone, phensuximide, methsuximide, alpha-methyl-alpha-phenylsuccinimide, and high concentrations of clonazepam are anticonvulsant drugs that preferentially prevent maximal electroshock seizures (MES) and generalized tonic-clonic convulsions; all these agents inhibit veratridine-induced accumulation of both cyclic AMP and cyclic GMP. In contrast, ethosuximide, trimethadione, valproic acid, and low concentrations of clonazepam are anticonvulsant drugs that act predominantly against Metrazol and absence seizures; these agents are ineffective or inhibit accumulation of only cyclic GMP. The results suggest that inhibition of cyclic AMP and cyclic GMP accumulation in depolarized brain tissue is a molecular neuropharmacological action characteristic of anticonvulsant drugs that have direct effects on cellular membrane function and prevent MES. Anticonvulsant drugs that do not inhibit accumulation of both cyclic AMP and cyclic GMP in depolarized brain tissue preferent...Continue Reading

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Citations

Apr 1, 1976·Journal of Neurochemistry·J A FerrendelliD A Kinscherf
Sep 1, 1977·Epilepsia·J A Ferrendelli, D A Kinscherf
Jan 1, 1972·Archives of Neurology·J H Pincus
Jul 1, 1972·Proceedings of the National Academy of Sciences of the United States of America·R J LipickyI M Stillman

Related Concepts

Anticonvulsants
Brain
Cyclic AMP, (R)-Isomer
Non-epileptic Convulsion
Neurohormones
Pentazol
Cyclic GMP
Seizures
Thrombocytopenia, Cyclic

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