Carbamazepine blocks NMDA-activated currents in cultured spinal cord neurons.
The antiepileptic agents, carbamazepine and phenytoin, suppress seizures in man and convulsant-induced hyperactivity in spinal cord nerve cell cultures. In the present study, we have shown by whole cell recording that carbamazepine, in contrast to phenytoin, blocks N-methyl-D-aspartate (NMDA)-activated membrane currents in cultured neurons in a dose-dependent fashion. The NMDA receptor-activated channel, which is blocked at physiological concentrations of Mg2+ at resting membrane potential, can be activated by glutamate in depolarized neurons and thus be involved in epileptogenesis. Therefore, the block of NMDA-evoked membrane currents in cultured neurons may contribute to the clinical effectiveness of carbamazepine.
Lampe
H
H
Department of Pharmacology and Toxicology, Medical School of Hannover, FRG.
Bigalke
H
H
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D002220:Carbamazepine / Q000494:pharmacology*; D002478:Cells, Cultured; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004594:Electrophysiology; D005260:Female; D007473:Ion Channels / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010672:Phenytoin / Q000494:pharmacology; D011247:Pregnancy; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology*
D000596:Amino Acids; D007473:Ion Channels; D002220:Carbamazepine; D010672:Phenytoin; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; C031231:2-amino-7-phosphonoheptanoic acid