Effects of anticonvulsants on responses to excitatory amino acids applied topically to rat cerebral cortex.
1. Five clinically used anticonvulsants were examined to find out if they block the effects of excitatory amino acids in the cerebral cortex of urethane anaesthetised rats. 2. Compounds were tested by topical application to the cortical surface and following their intraperitoneal injection at anticonvulsant doses. 3. Pentobarbital and diphenylhydantoin blocked the effect of quisqualic acid but only at concentrations higher than the therapeutically relevant levels. 4. Pentobarbital and diphenylhydantoin did not alter the effects of N-methyl-D,L-aspartic acid (NMDLA) or kainic acid. 5. Diazepam prevented the kainic acid-induced development of distorted somatosensory evoked potentials (SEPs) at therapeutically relevant levels. 6. Diazepam had no effect on NMDLA or quisqualic acid. 7. Carbamazepine and chlormethiazole had no effect on NMDLA, kainic acid or quisqualic acid. 8. The anticonvulsive effects of these drugs, with the exception of diazepam, probably do not involve antagonism of endogenous EAAs.
Department of Physiology, St George's Hospital Medical School, London.
J I
JI
Addae
T W
TW
Stone
D000287:Administration, Topical; D000596:Amino Acids / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D002220:Carbamazepine / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects*; D002719:Chlormethiazole / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000596:Amino Acids; D000927:Anticonvulsants; D002719:Chlormethiazole; D002220:Carbamazepine; D010672:Phenytoin; D010424:Pentobarbital; D003975:Diazepam