Neuroprotection by (-)-deprenyl
and related compounds

by
Maruyama W, Naoi M
Department of Basic Gerontology,
National Institute for Longevity Sciences,
Obu, Japan.
maruyama@nils.go.jp
Mech Ageing Dev 1999 Nov; 111(2-3):189-200


ABSTRACT

There is an increasing number of data by in vitro and in vivo experiments, indicating that (-)-deprenyl is neuroprotective to dopamine neurons, even though detailed mechanism remains to be clarified. In this paper neuroprotection by (-)-deprenyl and structurally related compounds was examined in concern with the suppression of apoptosis induced by a reactive oxygen species, peroxynitrite generated from SIN-1. The apoptotic DNA damage was quantitatively determined using dopaminergic SH-SYSY cells and by a single cell gel electrophoresis (comet) assay. DNA damage induced by peroxynitrite was proved to be apoptotic by prevention of the damage by cycloheximide or actinomycin-D. (-)-Deprenyl and other propargylamines protected the cells from apoptosis in a dose-dependent way. (-)-Deprenyl protected the cells even after it was washed out, suggesting that it may initiate the intracellular process to repress the apoptotic death program. The study on the structure-activity relationship of (-)-deprenyl analogues revealed that a N-propargyl residue with adequate size of hydrophobic structure is essentially required for the anti-apoptotic activity. These results suggest that (-)-deprenyl and related compounds may protect neurons from apoptosis and be applicable to delay the deterioration of neurons during advancing ageing and in neurodegenerative disorders.

MPP+
Apoptosis
Rasagiline
Metabolites
Interactions
MPP+/apoptosis
Phenylethylamine
The cheese effect
Retinal protection
Parkinson's disease
Alzheimer's disease
Desmethylselegiline
Selegiline and the brain
Apoptotic/anti-apoptotic
Selegiline and nitric oxide
Selegiline for longer-lived flies
Selegiline and life-expectancy
Selegiline as an immunostimulant
Selegiline for cocaine-dependence


Refs
and further reading

HOME
HedWeb
Nootropics
Cocaine.org
Future Opioids
BLTC Research
MDMA/Ecstasy
Superhapiness?
Utopian Surgery?
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
Critique of Huxley's Brave New World

The Good Drug Guide
The Good Drug Guide

The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family