CGS 19755 is a potent and competitive antagonist at NMDA-type receptors.
The N-Methyl-D-aspartate (NMDA)-type receptor blocking properties of CGS 19755, a novel, rigid analog of 2-amino-5-phosphonopentanoate, were demonstrated in vitro by the ability of the compound to block NMDA-evoked [3H]acetylcholine release (pA2 = 5.93). CGS 19755 (0.045 and 0.224 mmol/kg i.p.) was shown to be active in vivo as well by its ability to block harmaline-induced increases in cerebellar cGMP. Finally, CGS 19755 blocked sound-induced seizures in DBA/2 mice completely at doses of 1.0 nmol i.c.v. or 0.1 mmol/kg i.p. Taken together, these data indicate that CGS 19755 is a potent and competitive NMDA antagonist in vitro which is also active in vivo.
Lehmann
J
J
Research Department, Pharmaceuticals Division, Ciba-Geigy Corporation, Summit, NJ.
Chapman
A G
AG
Meldrum
B S
BS
Hutchison
A
A
Tsai
C
C
Wood
P L
PL
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D001667:Binding, Competitive; D001812:Blood-Brain Barrier; D002531:Cerebellum / Q000032:analysis; D006152:Cyclic GMP / Q000032:analysis; D006246:Harmaline / Q000494:pharmacology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D016202:N-Methylaspartate; D010875:Pipecolic Acids; D010880:Piperidines / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D012640:Seizures / Q000517:prevention & control
D010875:Pipecolic Acids; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D001224:Aspartic Acid; C053672:selfotel; D016202:N-Methylaspartate; D006246:Harmaline; D006152:Cyclic GMP; D000109:Acetylcholine