NeuropharmacologyThe putative cognitive enhancer KA-672. HCl is an uncompetitive voltage-dependent NMDA receptor antagonistLishko, Polina V.1; Maximyuk, Oleksandr P.1; Chatterjee, Shyam S.2; Nöldner, Michael2; Krishtal, Oleg A.1,3Author Information 1Department of Cellular Membranology, A.A. Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Bogomoletz str. 4, Kyiv 252601, Ukraine, Germany 2Present address: Dr. Willmar Schwabe GmbH & Co., Department of Pharmacology, Willmar-Schwabe-Str.4, 762227 Karlsruhe, Germany 3Corresponding Author: Oleg A. Krishtal ACKNOWLEDGEMENTS: This work was partially supported by INTAS (grant 96- 1493), and by the International Research Scholars grant from the Howard Hughes Medical Institute (grant 75195-458001). P.L. was supported by a personal Soros grant PSU074006. Received 23 September 1998; accepted 16 October 1998 NeuroReport: December 21st, 1998 - Volume 9 - Issue 18 - p 4193-4197 Buy Abstract KA-672.HCl (KA-672) is a new substance demonstrating anti-dementia properties. It shows modulatory effects on several neurotransmitter systems known to be affected in patients with Alzheimer's disease. In this study the action of KA-672 on the NMDA receptors was examined by applying patch clamp techniques to acutely isolated hippocampal neurons. KA-672 antagonizes NMDA responses 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 μM. This action of KA-672 is independent on the concentration either of agonist or coagonist 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 receptor-operated channel blocker. This property may account for its pharmacological profile. © 1998 Lippincott Williams & Wilkins, Inc.