CGS 19755 is a potent and competitive antagonist at NMDA-type receptors

Abstract

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 (pA 2 = 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.