In vivo neurochemical effects of the acetylcholinesterase inhibitor ENA713 in rat hippocampus.
Oral ENA713 (0.5, 1.5 and 4.5 mg/kg), an acetylcholinesterase inhibitor (AChEI), dose-dependently enhanced extracellular acetylcholine concentrations in the hippocampus of freely moving rats. This effect was paralleled by changes in both noradrenergic and dopaminergic transmission. In particular, ENA713 significantly decreased noradrenaline concentrations, whereas it significantly increased homovanillic acid levels, without affecting dopamine concentrations. Neither serotonin nor gamma-aminobutyric acid levels were modified by ENA713. These findings extend the neurochemical profile of ENA713 and suggest that it could be useful for the treatment of Alzheimer-type dementia which is associated with multiple neurotransmitter abnormalities in the brain.
Trabace
L
L
Department of Pharmacology and Human Physiology, Medical School, University of Bari, Policlinico-Piazza Giulio Cesare 11 70124, Bari, Italy.
Coluccia
A
A
Gaetani
S
S
Tattoli
M
M
Cagiano
R
R
Pietra
C
C
Kendrick
K M
KM
Cuomo
V
V
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002219:Carbamates / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D048448:Phenylcarbamates; D051381:Rats; D017208:Rats, Wistar; D000068836:Rivastigmine; D012701:Serotonin / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000187:drug effects / Q000378:metabolism
D002219:Carbamates; D002800:Cholinesterase Inhibitors; D048448:Phenylcarbamates; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D000109:Acetylcholine; D000068836:Rivastigmine; D004298:Dopamine; D009638:Norepinephrine