TY - JOUR
T1 - Anti-apoptotic action of anti-Alzheimer drug, TV3326 [(N-propargyl)-(3R)-aminoindan-5-yl]-ethyl methyl carbamate, a novel cholinesterase-monoamine oxidase inhibitor
AU - Maruyama, Wakako
AU - Weinstock, Marta
AU - Youdim, Moussa B.H.
AU - Nagai, Masayo
AU - Naoi, Makoto
PY - 2003/5/8
Y1 - 2003/5/8
N2 - The anti Parkinson drug, rasagiline [R-(+)-N-propargyl-1-aminoindan], an inhibitor of type B monoamine oxidase, has been shown to suppress apoptosis induced by neurotoxins and oxidative stress. A series of novel propargylaminoindans with a carbamate moiety to inhibit cholinesterase were developed from phamacophore of rasagiline to protect or rescue deteriorated neurons in Alzheimer's and Lewy Body disease and provide a beneficial effect on the cognitive deficits. Rasagiline analogues were found to protect dopaminergic SH-SY5Y cells against apoptosis induced by peroxynitrite donor. SIN-1. TV3326, [(N-propargyl)-(3R)-aminoindan-5-yl]-ethyl methyl carbamate, was as effective as rasagiline in preventing apoptosis, followed by its S-enantiomer, TV3279. The anti-apoptotic-neuroprotective activity was shown to reside in the propargylamine and not the carbamate moiety. This resulted in stabilization of the mitochondrial membrane potential, the collapse of which initiates the apoptotic cascade.
AB - The anti Parkinson drug, rasagiline [R-(+)-N-propargyl-1-aminoindan], an inhibitor of type B monoamine oxidase, has been shown to suppress apoptosis induced by neurotoxins and oxidative stress. A series of novel propargylaminoindans with a carbamate moiety to inhibit cholinesterase were developed from phamacophore of rasagiline to protect or rescue deteriorated neurons in Alzheimer's and Lewy Body disease and provide a beneficial effect on the cognitive deficits. Rasagiline analogues were found to protect dopaminergic SH-SY5Y cells against apoptosis induced by peroxynitrite donor. SIN-1. TV3326, [(N-propargyl)-(3R)-aminoindan-5-yl]-ethyl methyl carbamate, was as effective as rasagiline in preventing apoptosis, followed by its S-enantiomer, TV3279. The anti-apoptotic-neuroprotective activity was shown to reside in the propargylamine and not the carbamate moiety. This resulted in stabilization of the mitochondrial membrane potential, the collapse of which initiates the apoptotic cascade.
KW - Alzheimer's disease
KW - Anti-apoptotic activity
KW - Cholinesterase inhibitor
KW - Lewy Body disease
KW - Mitochondrial membrane potential
KW - Monoamine oxidase inhibitor
KW - Parkinson's disease
KW - Peroxynitrite
KW - Propargylamines
KW - Rasagiline
KW - TV3326
UR - http://www.scopus.com/inward/record.url?scp=0345237921&partnerID=8YFLogxK
U2 - 10.1016/S0304-3940(03)00211-8
DO - 10.1016/S0304-3940(03)00211-8
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C2 - 12697291
AN - SCOPUS:0345237921
SN - 0304-3940
VL - 341
SP - 233
EP - 236
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 3
ER -