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NEUROLOGY 1976;26:162
© 1976 American Academy of Neurology

Mechanism of action of anticonvulsants

Role of the differential effects on the active uptake of putative neurotransmitters

J. WEINBERGER, M.D., W. J. NICKLAS, Ph.D. and S. BERL, M.D.

From the Department of Neurology, Mount Sinai School of Medicine, New York.

The effect of pentobarbital and phenytoin on the high-affinity uptake of the putative neurotransmitters gamma-aminobutyric acid (GABA), glutamate, and norepinephrine was examined in synaptosomes prepared from rat brain. Both pentobarbital and phenytoin inhibited the uptake of norepinephrine. Pentobarbital increased the uptake of GABA twofold and only slightly increased the uptake of glutamate. Phenytoin facilitated GABA uptake to a lesser extent than did pentobarbital, but also increased the uptake of glutamate. This suggests that these drugs may limit the propagation of seizures through the balance of excitatory glutamate pathways and inhibitory GABA and norepinephrine pathways. The contrasting effects of these drugs on GABA and glutamate uptake may be related to the hypnotic properties of pentobarbital not present in phenytoin.

Reprint requests should be addressed to Dr. Nicklas at Department of Neurology, Mount Sinai School of Medicine, Fifth Avenue and 100th Street, New York, NY 10029.

This work was supported in part by NIH grants MH-25505, NS-11824, Clinical Center of Research on Parkinson's and Allied Diseases, NS-11631, and training grant 5 T01 NS05072.

Received for publication June 5, 1975.






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