Pro-convulsant actions of theophylline and caffeine in the hippocampus: implications for the management of temporal lobe epilepsy.
The pro-convulsant actions of theophylline and caffeine have been investigated using the hippocampal slice preparation and rats administered kainic acid or Metrazol. Both theophylline and caffeine induced the generation of epileptiform activity in the CA3 region of the hippocampal slice with convulsive dose50 (CD50) values of 3 microM respectively. Kainic acid-induced bursting in hippocampal slices was enhanced by theophylline (0.3-30 microM) and caffeine (1-100 microM). Theophylline induced burst firing in response to electrical stimulation in hippocampal area CA3 but not area CA1. Theophylline (50 mg/kg) strongly potentiated the effect of the limbic convulsant kainic acid in vivo whilst a dose of 200 mg/kg was necessary to significantly lower the threshold dose of Metrazol required to induce generalized convulsions. We conclude that alkylxanthines, probably by antagonizing the effect of endogenous adenosine, exert a pro-convulsant action in the hippocampus which preferentially promotes limbic seizures.
Department of Pharmacology, Wellcome Research Laboratories, Burroughs Wellcome Co., Research Triangle Park, NC 27709.
B
B
Ault
M A
MA
Olney
J L
JL
Joyner
C E
CE
Boyer
M A
MA
Notrica
F E
FE
Soroko
C M
CM
Wang
D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D003292:Convulsants; D004347:Drug Interactions; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced; D005260:Female; D006624:Hippocampus / Q000187:drug effects*; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D010433:Pentylenetetrazole / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000187:drug effects; D013806:Theophylline / Q000494:pharmacology*
D003292:Convulsants; D011983:Receptors, Purinergic; D002110:Caffeine; D013806:Theophylline; D007608:Kainic Acid; D010433:Pentylenetetrazole