Reduced taurine contents and modification of anticonvulsive effects of phenobarbital and phenytoin by guanidinoethane sulfonate in mice.
In the present study, we investigated whether administration of guanidinoethane sulfonate, and inhibitor of taurine uptake, worsens electroshock-induced convulsions or modifies the antiepileptic actions of phenobarbital or phenytoin against maximal electroshock seizures in mice. Treatment with 1% guanidinoethane sulfonate in drinking water for 9 days decreased taurine concentration in the brain to 76% of control value. Under these conditions, neither the severity of tonic convulsions of maximal electroshock seizures nor the threshold for tonic extension caused by electroshock was altered. On the other hand, the antiepileptic potency of phenobarbital and phenytoin against tonic convulsions of maximal electroshock seizures in mice was significantly lessened by chronic administration of guanidinoethane sulfonate. This decrease in potency was not due to an alteration in pharmacokinetics, as the brain levels of these drugs were unchanged. Furthermore, administration of the anticonvulsive drugs did not change brain concentrations of guanidinoethane sulfonate and total guanidino compounds. It is suggested that the observed loss of anticonvulsive potency of phenobarbital and phenytoin may be related to the decreased concentration of taurine produced by administration of guanidinoethane sulfonate.
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D051381:Rats; D012640:Seizures / Q000188:drug therapy / Q000209:etiology; D013654:Taurine / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology
D000596:Amino Acids; D000927:Anticonvulsants; D013654:Taurine; C009558:taurocyamine; D010672:Phenytoin; D010634:Phenobarbital