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

Polina V. Lishko; Oleksandr P. Maximyuk; Shyam S. Chatterjee; Michael Nöldner; Oleg A. Krishtal

doi:10.1097/00001756-199812210-00035

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

Polina V. Lishko, Oleksandr P. Maximyuk, Shyam S. Chatterjee, Michael Nöldner, Oleg A. Krishtal

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

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.

Original language	English
Pages (from-to)	4193-4197
Number of pages	5
Journal	NeuroReport
Volume	9
Issue number	18
DOIs	https://doi.org/10.1097/00001756-199812210-00035
State	Published - Dec 21 1998

Keywords

Alzheimer's disease
Concentration clamp
Dementia
Hippocampal neurons
KA-672.HCl
Neuroprotection
NMDA receptor antagonist

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10.1097/00001756-199812210-00035

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

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.",

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AU - Lishko, Polina V.

AU - Maximyuk, Oleksandr P.

AU - Chatterjee, Shyam S.

AU - Nöldner, Michael

AU - Krishtal, Oleg A.

PY - 1998/12/21

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N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Concentration clamp

KW - Dementia

KW - Hippocampal neurons

KW - KA-672.HCl

KW - Neuroprotection

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ER -

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

Abstract

Keywords

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