ANTICONVULSANT PROPERTIES OF NONCOMPETITIVE ANTAGONISTS OF THE N-METHYL-D-ASPARTATE RECEPTOR IN GENETICALLY EPILEPSY-PRONE RATS - COMPARISON WITH CPPENE

被引:58
作者
DESARRO, GB [1 ]
DESARRO, A [1 ]
机构
[1] UNIV MESSINA,FAC MED,INST PHARMACOL,I-98100 MESSINA,ITALY
关键词
EPILEPSY; NMDA RECEPTOR ANTAGONISTS; ANTICONVULSANTS; AUDIOGENIC SEIZURES; GENETICALLY EPILEPSY-PRONE RATS;
D O I
10.1016/0028-3908(93)90129-Q
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Some non-competitive antagonists of N-methyl-D-aspartate (NMDA) were evaluated for potency to antagonize audiogenic seizures in genetically epilepsy-prone rats, following intraperitoneal administration. Phencyclidine (PCP), dizocilpine (MK-801), ketamine, ifenprodil and dextromethorphan, displayed anticonvulsant activity at doses similar to those which impaired performance in the rotarod equilibrium procedure, The noncompetitive NMDA receptor antagonists, at doses which slightly overlapped with the doses required for a full anticonvulsant protection against audiogenic seizures in genetically epilepsy-prone rats, induced profound untoward behavioural effects. This behavioural syndrome was characterized by marked ataxia, hyperactivity, stereotypes and wet dog shakes. In contrast, the effective anticonvulsant dose of 3-(2-carboxypiperazin-4-yl)propenyl-1-phosphonic acid (CPPene) was less than that required to impair rotarod performance and did not produce the PCP-like syndrome. A potential use in antiepileptic therapy, of CPPene or other new selective NMDA antagonists, with fewer neurotoxic effects but not for non-competitive antagonists such as MK-801, is suggested.
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页码:51 / 58
页数:8
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