Novel kainic acid analogues. Effects on cyclic GMP content of adult rat cerebellar slices.
On the basis of previous electrophysiological studies, it has been proposed that there are three main classes of excitatory amino acid receptor in the mammalian central nervous system, which are activated preferentially by kainic acid, quisqualic acid and N-methyl-D-aspartate respectively. Although the pharmacology of the N-methyl-D-aspartate receptor has been investigated extensively, potent and selective ligands which act at the kainate or quisqualate sites are lacking. In this study, we report that a number of novel kainate analogues possess either agonist or antagonist activity in a system which permits investigation of receptor-mediated coupled responses, viz. the ability of excitatory amino acids to elevate cyclic GMP concentrations in incubated cerebellar slices prepared from the adult rat. The data reported here provide some clues as to the likely structural requirements for developing effective kainate antagonists.
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002531:Cerebellum / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate; D010069:Oxadiazoles / Q000494:pharmacology; D016318:Quisqualic Acid; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D013329:Structure-Activity Relationship
D010069:Oxadiazoles; D017981:Receptors, Neurotransmitter; D001224:Aspartic Acid; D016202:N-Methylaspartate; D016318:Quisqualic Acid; D006152:Cyclic GMP; D007608:Kainic Acid; D002118:Calcium