7-Chlorokynurenic acid, a strychnine-insensitive glycine receptor antagonist, inhibits limbic seizure kindling.
Electrical kindling of the rat amygdala was performed following daily intra-amygdaloid injections of the strychnine-insensitive glycine receptor antagonist 7-chlorokynurenic acid (7-CIKYN) (10 nmol), 7-CIKYN (10 nmol) plus glycine (40 nmol), or vehicle alone. Control (vehicle-treated) animals showed their first fully kindled (Stage 5) seizure after 9.5 +/- 0.8 daily stimulations. Animals pretreated with 7-CIKYN (10 nmol) showed a significant retardation of development of both the electroencephalographic and motor (17.7 +/- 2.9 daily stimulations) components of the seizure response. This inhibitory influence of 7-CIKYN was blocked when glycine (40 nmol) was co-injected daily with the antagonist. The mean initial afterdischarge threshold (ADT) was unaffected by pretreatment with 7-CIKYN (10 nmol). These results provide the first demonstration of an antiepileptogenic action of a strychnine-insensitive glycine receptor antagonist. They further support a key involvement of NMDA receptors in generative mechanisms of epilepsy.
Croucher
M J
MJ
Department of Biochemistry, Imperial College of Science, Technology and Medicine, London, U.K.
Bradford
H F
HF
D000679:Amygdala / Q000502:physiology; D000818:Animals; D000927:Anticonvulsants; D004558:Electric Stimulation; D007696:Kindling, Neurologic / Q000187:drug effects*; D007736:Kynurenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008032:Limbic System / Q000502:physiology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D012640:Seizures / Q000503:physiopathology / Q000517:prevention & control*; D013331:Strychnine / Q000494:pharmacology
D000927:Anticonvulsants; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D007736:Kynurenic Acid; D013331:Strychnine; C057013:7-chlorokynurenic acid