Anticonvulsant effects of dizocilpine against picrotoxin-induced seizure activity in vivo and in vitro.
The effects of dizocilpine on picrotoxin (PTX)-induced generalized tonic-clonic (GTC) seizures in vivo and PTX-induced epileptiform activity in vitro brain slices were studied. Groups of rats were pretreated intraperitoneally with dizocilpine or a control saline vehicle. Twenty minutes later, subgroups within each pretreatment group were injected subcutaneously with different doses of PTX. The results showed that dizocilpine significantly increases the mean latency period from administration to GTC seizures and reduces the incidence of death. Intracellular recording techniques were used to examine the mechanism underlying the anticonvulsant action of dizocilpine on the amygdala. A superfusion of dizocilpine reduced the evoked burst duration by an average of 35%. The synaptic response, mediated by the N-methyl-D-aspartate (NMDA) receptor, was isolated by application of a solution containing the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and GABAA blocker PTX. A superfusion of dizocilpine blocked NMDA receptor-mediated synaptic excitation. These results suggest that the anticonvulsant effect of dizocilpine is likely due to its blocking action on the NMDA receptors.
Gean
P W
PW
Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan, Taiwan, R.O.C.
Lin
J H
JH
Huang
C C
CC
Kuo
J R
JR
D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology / Q000627:therapeutic use*; D004829:Epilepsy, Generalized / Q000139:chemically induced / Q000188:drug therapy*; D010852:Picrotoxin; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects
D016291:Dizocilpine Maleate; D010852:Picrotoxin; D016194:Receptors, N-Methyl-D-Aspartate