Anti-apoptotic action of anti-Alzheimer drug, TV3326 [(N-propargyl)-(3R)-aminoindan-5-yl]-ethyl methyl carbamate, a novel cholinesterase-monoamine oxidase inhibitor

Wakako Maruyama, Marta Weinstock, Moussa B.H. Youdim, Masayo Nagai, Makoto Naoi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

97 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)233-236
Number of pages4
JournalNeuroscience Letters
Volume341
Issue number3
DOIs
StatePublished - 8 May 2003

Keywords

  • Alzheimer's disease
  • Anti-apoptotic activity
  • Cholinesterase inhibitor
  • Lewy Body disease
  • Mitochondrial membrane potential
  • Monoamine oxidase inhibitor
  • Parkinson's disease
  • Peroxynitrite
  • Propargylamines
  • Rasagiline
  • TV3326

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