Effects of nefiracetam on amnesia animal models with neuronal dysfunctions

Masayuki Hiramatsu, Tadashi Shiotani, Tsutomu Kameyama, Toshitaka Nabeshima

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The effects of N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide (nefiracetam; DM-9384), on learning and memory in several amnesia animal models with neuronal dysfunctions were investigated. Nefiracetam improved scopolamine-, bicuculline-, picrotoxin-, ethanol-, chlordiazepoxide- and cycloheximide-induced amnesia. Anti-amnesic action of nefiracefam on scopolamine model was antagonized by nifedipine and flunarizine, but not by diltiazem. Repeated administration of nefiracetam to AF64A-treated animals improved impairment of learning and memory as well as the alterations in cholinergic and monoaminergic neurotransmitters in the hippocampus. Basal forebrain (BF) lesioned rats induced by excitotoxin or by thermal coagulation showed impairment of learning accompanied by a marked reduction in choline acetyltransferase (ChAT) and acetylcholine esterase activities. Nefiracetam improved the learning deficit of the BF-lesioned rats. Nefiracetam also improved the carbon monoxide-induced delayed and acute amnesia. Nefiracetam stimulated acetylcholine release in the frontal cortex. Repeated administration of nefiracetam increased ChAT activity, γ-aminobutyric acid (GABA) turnover and glutamic acid decarboxylase activity, and facilitated the Na+-dependent high-affinity GABA uptake. Nefiracetam activated the high voltage-activated (N/L-type) Ca2+ channel. The dose-response curves of nefiracetam were bell-shaped in both behavioral and biochemical studies. Therefore, it is suggested that nefiracetam improves the dysfunction of cholinergic, GABAergic and/or monoaminergic neuronal function by acting at Ca2+ channel and enhancing the release of neurotransmitters, and modifies impairment of memory processes induced by drugs and hypoxia.

Original languageEnglish
Pages (from-to)107-115
Number of pages9
JournalBehavioural Brain Research
Volume83
Issue number1-2
DOIs
Publication statusPublished - 01-02-1997
Externally publishedYes

Fingerprint

Amnesia
Animal Models
Learning
Scopolamine Hydrobromide
Choline O-Acetyltransferase
gamma-Aminobutyric Acid
Cholinergic Agents
Acetylcholine
Neurotransmitter Agents
nefiracetam
Flunarizine
Aminobutyrates
Chlordiazepoxide
Picrotoxin
Glutamate Decarboxylase
Bicuculline
Diltiazem
Neurotoxins
Frontal Lobe
Esterases

All Science Journal Classification (ASJC) codes

  • Behavioral Neuroscience

Cite this

Hiramatsu, Masayuki ; Shiotani, Tadashi ; Kameyama, Tsutomu ; Nabeshima, Toshitaka. / Effects of nefiracetam on amnesia animal models with neuronal dysfunctions. In: Behavioural Brain Research. 1997 ; Vol. 83, No. 1-2. pp. 107-115.
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Effects of nefiracetam on amnesia animal models with neuronal dysfunctions. / Hiramatsu, Masayuki; Shiotani, Tadashi; Kameyama, Tsutomu; Nabeshima, Toshitaka.

In: Behavioural Brain Research, Vol. 83, No. 1-2, 01.02.1997, p. 107-115.

Research output: Contribution to journalArticle

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