The putative cognitive enhancer KA-672.HCl is an uncompetitive voltage-dependent NMDA receptor antagonist

KA-672.HCl (KA-672) is a new substance demonstrating anti-dementia properti es. It shows modulatory effects on several neurotransmitter systems known t o be affected in patients with Alzheimer's disease. In this study the actio n of KA-672 on the NMDA receptors was examined by applying patch clamp tech niques to acutely isolated hippocampal neurons. KA-672 antagonizes NMDA res ponses in a voltage-dependent manner. At a holding potential of -90 mV the IC50 value for the blocking action of KA-672 was 20 +/- 7 mu M This action of KA-672 is independent on the concentration either of agonist or coagonis t of NMDA receptor. Ketamine, which interacts with the PCP center, does not occlude the action of KA-672. Evidently, KA-672.HCl is a weak NMDA recepto r-operated channel blocker. This property may account for its pharmacologic al profile. (C) 1998 Lippincott Williams & Wilkins.