Effects of phenytoin on the amygdala neurons in vitro.
The present study was aimed at elucidating the possible mechanisms underlying the anticonvulsant efficacy of phenytoin using intracellular recording techniques in the in vitro amygdalar slice preparation. Synaptic response mediated by the N-methyl-D-aspartate (NMDA) receptor (EPSPNMDA) was isolated pharmacologically by application of a solution containing non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (10 mumol/l) and gamma-aminobutyric acidA receptor antagonist bicuculline (20 mumol/l). Phenytoin inhibits the amplitude of EPSPNMDA without affecting the postsynaptic depolarization induced by exogenous application of NMDA. In addition, phenytoin increases the magnitude of paired-pulse facilitation which is consistent with a presynaptic mode of action. These results suggest that inhibition of transmitter release due to presynaptic blockade of Na+ and/or Ca2+ channels may account largely for the anticonvulsant efficacy of phenytoin.
Cheng
L L
LL
Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan City, Taiwan.
Wang
S J
SJ
Tsai
J J
JJ
Gean
P W
PW
D000679:Amygdala / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010672:Phenytoin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000927:Anticonvulsants; D018690:Excitatory Amino Acid Agonists; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D005680:gamma-Aminobutyric Acid; D010672:Phenytoin; D016202:N-Methylaspartate; D002118:Calcium