Effects of ENA713 and CHF2819, two anti-Alzheimer's disease drugs, on rat amino acid levels.
The effects of oral ENA713 and CHF2819 (0.5, 1.5 and 4.5 mg/kg), two novel acetylcholinesterase inhibitors, on extracellular concentrations of amino acids in rat hippocampus, were evaluated using in vivo microdialysis. ENA713, at 4.5 mg/kg, but not CHF2819, significantly decreased glutamate, taurine, arginine and citrulline levels, without affecting aspartate concentrations. These results suggest that the modulation of amino acidergic transmission could represent an additional mechanism of action in Alzheimer's disease for some acetylcholinesterase inhibitors.
Trabace
L
L
Department of Pharmacology and Human Physiology, Medical School, University of Bari, Policlinico, Piazza Giulio Cesare, 70124 Bari, Italy. trabace@farmacol.uniba.it
Cassano
T
T
Cagiano
R
R
Tattoli
M
M
Pietra
C
C
Steardo
L
L
Kendrick
K M
KM
Cuomo
V
V
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001120:Arginine / Q000378:metabolism; D001224:Aspartic Acid / Q000378:metabolism; D002219:Carbamates / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D002956:Citrulline / Q000378:metabolism; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018846:Excitatory Amino Acids / Q000378:metabolism*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D048448:Phenylcarbamates; D051381:Rats; D017208:Rats, Wistar; D000068836:Rivastigmine; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013654:Taurine / Q000378:metabolism
D002219:Carbamates; D002800:Cholinesterase Inhibitors; D003497:Cyclic N-Oxides; D018846:Excitatory Amino Acids; D048448:Phenylcarbamates; D013654:Taurine; D002956:Citrulline; D001224:Aspartic Acid; D018698:Glutamic Acid; D001120:Arginine; C410961:CHF 2819; D000068836:Rivastigmine