CGP 31358 binds to a site on the NMDA receptor that is coupled to both the transmitter recognition site and the channel domain.
CGP 31358, a novel triazole, inhibited the binding of L-[3H]glutamate and [3H]MK-801 to the N-methyl-D-aspartate (NMDA) receptor complex in rat brain synaptic membrane fractions, and showed anticonvulsant activity in mice. It had no effect on the strychnine-insensitive binding of [3H]glycine. Saturation and Hill analyses indicated that CGP 31358 binds to a site on the NMDA receptor which is separate from, but coupled to, both the transmitter recognition site and the channel domain. Available data indicate that this site is distinct from those with which tricyclic antidepressants and ifenprodil interact. CGP 31358 is a new chemical entity with a novel mechanism of action at the NMDA receptor, and as such may form a tool for understanding the molecular pharmacology of this receptor-channel complex.
Baud
J
J
Pharmaceuticals Division, Ciba-Geigy Ltd., Basel, Switzerland.
Thedinga
K
K
Portet
C
C
Schmutz
M
M
Bittiger
H
H
Bischoff
S
S
Hauser
K
K
Benedict
M
M
Meier
R
R
Fagg
G E
GE
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003986:Dibenzocycloheptenes / Q000378:metabolism; D016291:Dizocilpine Maleate; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D051379:Mice; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology* / Q000627:therapeutic use
D000927:Anticonvulsants; D003986:Dibenzocycloheptenes; D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D014230:Triazoles; C062874:CGP 31358; D018698:Glutamic Acid; D016291:Dizocilpine Maleate