Analysis of carbamazepine's anticonvulsant actions in hippocampal and amygdaloid slices of the rat.
The mechanism of action of the anticonvulsant drug carbamazepine was studied in rat hippocampal and amygdaloid slices using intracellular recording techniques. Stimulation of the Schaffer collateral/commissural pathway evoked an excitatory postsynaptic potential (EPSP) in CA1 pyramidal cells. Thirty minutes after superfusing with Mg(++)-free solution, the same stimulus intensity triggered burst firing. Application of carbamazepine reversibly reduced the burst duration in a dose-dependent manner. Synaptic response mediated by the N-methyl-D-aspartate (NMDA) receptors (EPSPNMDA) was isolated pharmacologically by application of a solution containing non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX,10 microM) and gamma-aminobutyric acidA receptor or antagonist picrotoxin (50 microM). Carbamazepine reversibly blocked the amplitude of EPSPNMDA in a concentration which did not affect the normal synaptic transmission. These results suggest that the combined blockade of NMDA receptors and firing of action potential forms the basis for the anticonvulsant effect of carbamazepine.
Gean
P W
PW
Department of Pharmacology, College of Medicine, National Cheng-Kung University Tainan City, Taiwan, Republic of China.
Huang
C C
CC
Kuo
J R
JR
Lin
J H
JH
Yi
P L
PL
Tsai
J J
JJ
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000679:Amygdala / Q000187:drug effects*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002220:Carbamazepine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D008274:Magnesium / Q000502:physiology; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010852:Picrotoxin / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000927:Anticonvulsants; D002220:Carbamazepine; D008274:Magnesium; D010852:Picrotoxin; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate