Effect of combination of dizocilpine with general antiepileptic drugs on amygdala kindling models in rats.
OBJECTIVE
To investigate the antiepileptic effect of dizocilpine (MK-801) on amygdala kindling models in rats and the effects of its combination with general antiepileptic drugs.


METHODS
To establish amygdala kindling models in rats and observe the effect of dizocilpine on kindling models and its combination with general antiepileptic drugs (phenobarbital, valproate and nicardipine) at ineffective dose. The influence of dizocilpine on convulsions induced by semicarbazide (SCZ) in mice were also observed.


RESULTS
Dizocilpine (0.1-0.25 mg.kg-1, i.p.) was shown to dose-dependently inhibit amygdala kindled seizure, shorten the after discharge duration (ADD) and reduce the Racine's stage (P < 0.01). The combination of dizocilpine with phenobarbital, valproate, nicardipine at ineffective dose shortened ADD or reduced Racine's stages (P < 0.01). Dizocilpine (0.1-0.25 mg.kg-1, i.p.) significantly prolonged the latency and reduced the rate of convulsions and death in mice.


CONCLUSIONS
Dizocilpine inhibits the seizure of the amygdala kindling and improve the antiepileptic activity of phenobarbital, valproate and nicardipine, indicating that these combination may provide a new approach for treating epilepsy.
Zhong
Wei-zhen
WZ
Department of Pharmacology, Medical College, Qingdao University, Qingdao 266021, China.
Zhao
Yong-juan
YJ
Gao
Gui-mei
GM
Yang
Zhi-hong
ZH
Yue
Wang
W
D000679:Amygdala / Q000187:drug effects / Q000503:physiopathology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D016291:Dizocilpine Maleate / Q000494:pharmacology* / Q000627:therapeutic use; D004558:Electric Stimulation; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy*; D005260:Female; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D051379:Mice; D009529:Nicardipine / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012663:Semicarbazides; D014635:Valproic Acid / Q000494:pharmacology
D000927:Anticonvulsants; D012663:Semicarbazides; C010059:carbamylhydrazine; D014635:Valproic Acid; D016291:Dizocilpine Maleate; D009529:Nicardipine; D010634:Phenobarbital