Involvement of cholinergic and GABAergic systems in the reversal of memory disruption by NS-105, a cognition enhancer.

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Ogasawara T, Itoh Y, Tamura M, Mushiroi T, Ukai Y, Kise M, Kimura K

Involvement of cholinergic and GABAergic systems in the reversal of memory disruption by NS-105, a cognition enhancer.

Pharmacol Biochem Behav. 1999 Sep;64(1):41-52.

PubMed ID

10494996 [ View in PubMed

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Abstract

The effects of (+)-5-oxo-D-prolinepiperidinamide monohydrate (NS-105) on the scopolamine-, electrolytic lesion of the nucleus basalis magnocellularis (NBM)-, AF64A-, baclofen-, cerebral ischemia- and electroconvulsive shock (ECS)-induced memory disruption in the passive avoidance response or radial arm maze tasks were investigated in rats. The effects of NS-105 were compared with those of aniracetam, bifemelane, idebenone, and indeloxazine in two tasks of the passive avoidance response. Furthermore, effects of NS-105 on in vivo release of acetylcholine (ACh) in the cerebral cortex, high-affinity choline uptake (HACU) of the cerebral cortex in rats with lesion of NBM, HACU of the hippocampus in rats treated with pentobarbital and activity of choline acetyltransferase (ChAT) of the cerebral cortex in rats with lesion of NBM were examined. NS-105 showed antiamnestic actions in a variety of animal models of cholinergic dysfunction employed in this study. Aniracetam improved memory disruption caused by scopolamine, but bifemelane, idebenone, and indeloxazine did not. NS-105 (10 mg/kg) showed the increase of ACh release from the cerebral cortex and the enhancement of HACU both in the cerebral cortex and hippocampus, but showed no change in activity of ChAT. NS-105 also reversed memory disruption induced by baclofen, a potent GABA(B) receptor agonist, but all of reference drugs did not. These results suggest that antiamnestic action of NS-105 is due to the facilitation of cholinergic neuronal activity and the suppression of GABA(B) receptor-mediated responses.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Arbaclofen	Gamma-aminobutyric acid type B receptor subunit 1	Protein	Humans	Yes	Agonist	Details
Arbaclofen Placarbil	Gamma-aminobutyric acid type B receptor subunit 1	Protein	Humans	Yes	Agonist	Details
Baclofen	Gamma-aminobutyric acid type B receptor subunit 1	Protein	Humans	Unknown	Agonist	Details