PT  - JOURNAL ARTICLE
AU  - J A Ferrendelli
AU  - D A Kinscherf
TI  - Similar effects of phenytoin and tetrodotoxin on cyclic nucleotid regulation in depolarized brain tissue.
DP  - 1978 Dec 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 787--793
VI  - 207
IP  - 3
4099  - http://jpet.aspetjournals.org/content/207/3/787.short
4100  - http://jpet.aspetjournals.org/content/207/3/787.full
SO  - J Pharmacol Exp Ther1978 Dec 01; 207
AB  - Veratridine, ouabain, glutamate and high concentrations of K+, agents which cause depolarization of excitable cells, markedly elevate levels of adenosine 3':5'-monophosphate (cyclic AMP) and guanosine 3':5'-monophosphate (cyclic GMP) in brain tissue, in vitro. Phenytoin inhibits veratridine (5 micron)- and ouabain (100 micron)-induced accumulations of both cyclic nucleotides in slices of mouse cerebral cortex. As little as 10 to 30 micron phenytoin produces a statistically significant depression, and 100 to 400 micron inhibits more than 90%. In contrast, at concentrations up to 400 micron, the drug has little or no effect on elevations of cyclic AMP or cyclic GMP caused by glutamate (10 mM) or K+ (64 mM). The inhibitory action of phenytoin on ouabain-induced elevations of cyclic nucleotides appears to be noncompetitive; inhibition of the veratridine effects probably is also noncompetitive. Tetrodotoxin also inhibits ouabain- and veratridine-induced elevations of cyclic nucleotides in brain slices, but it is 3 orders of magnitude more potent than phenytoin. Like phenytoin, tetrodotoxin does not inhibit the effects of glutamate or K+ on cyclic nucleotide regulation. These data suggest that, similar to tetrodotoxin phenytoin blocks sodium channels in excitable membranes. Possibly this mechanism is responsible for the antiepileptic action of phenytoin.