PMID- 10051141
DA - 19990503
DCOM- 19990503
LR - 20011128
IS - 0007-1188
VI - 126
IP - 1
DP - 1999 Jan
TI - Improvement by nefiracetam of beta-amyloid-(1-42)-induced learning and memory impairments in rats.
PG - 235-44 AB - 1. We have previously demonstrated that continuous i.c.v. infusion of amyloid beta-peptide (A beta), the major constituent of senile plaques in the brains of patients with Alzheimer's disease, results in learning and memory deficits in rats. 2. In the present study, we investigated the effects of nefiracetam [N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide, DM-9384] on A beta-(1-42)-induced learning and memory deficits in rats. 3. In the A beta-(1-42)-infused rats, spontaneous alternation behaviour in a Y-maze task, spatial reference and working memory in a water maze task, and retention of passive avoidance learning were significantly impaired as compared with A beta-(40-1)-infused control rats. 4. Nefiracetam, at a dose range of 1-10 mg kg(-1), improved learning and memory deficits in the A beta-(1-42)-infused rats when it was administered p.o. 1 h before the behavioural tests. 5. Nefiracetam at a dose of 3 mg kg(-1) p.o. increased the activity of choline acetyltransferase in the hippocampus of A beta-(1-42)-infused rats. 6. Nefiracetam increased dopamine turnover in the cerebral cortex and striatum of A beta-(1-42)-infused rats, but failed to affect the noradrenaline, serotonin and 5-hydroxyindoleacetic acid content. 7. These results suggest that nefiracetam may be useful for the treatment of patients with Alzheimer's disease.
AD - Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya
University School of Medicine, Japan.
FAU - Yamada, K
AU - Yamada K
FAU - Tanaka, T
AU - Tanaka T
FAU - Mamiya, T
AU - Mamiya T
FAU - Shiotani, T
AU - Shiotani T
FAU - Kameyama, T
AU - Kameyama T
FAU - Nabeshima, T
AU - Nabeshima T
LA - eng
PT - Journal Article
CY - ENGLAND
TA - Br J Pharmacol
JID - 7502536
RN - 0 (Amyloid beta-Protein)
RN - 0 (Biogenic Monoamines)
RN - 0 (Peptide Fragments)
RN - 0 (Psychotropic Drugs)
RN - 0 (Pyrrolidinones)
RN - 102-32-9 (3,4-Dihydroxyphenylacetic Acid)
RN - 306-08-1 (Homovanillic Acid)
RN - 51-61-6 (Dopamine)
RN - 77191-36-7 (nefiracetam)
RN - EC 2.3.1.6 (Choline O-Acetyltransferase)
SB - IM
MH - 3,4-Dihydroxyphenylacetic Acid/metabolism
MH - Amyloid beta-Protein/*pharmacology
MH - Animal
MH - Avoidance Learning/drug effects
MH - Biogenic Monoamines/metabolism
MH - Choline O-Acetyltransferase/drug effects/metabolism
MH - Corpus Striatum/drug effects/enzymology
MH - Dopamine/metabolism
MH - Frontal Lobe/drug effects/enzymology
MH - Hippocampus/drug effects/enzymology
MH - Homovanillic Acid/metabolism
MH - Learning/drug effects
MH - Learning Disorders/chemically induced/*drug therapy
MH - Male
MH - Maze Learning/drug effects
MH - Memory Disorders/chemically induced/*drug therapy
MH - Motor Activity/drug effects
MH - Peptide Fragments/*pharmacology
MH - Psychotropic Drugs/pharmacology/*therapeutic use
MH - Pyrrolidinones/pharmacology/*therapeutic use
MH - Rats
MH - Rats, Wistar
MH - Support, Non-U.S. Gov't
EDAT- 1999/03/02
MHDA- 1999/03/02 00:01
PST - ppublish
SO - Br J Pharmacol 1999 Jan;126(1):235-44.