Novel neuroprotective anti-Alzheimer drugs with anti-depressant activity derived from the anti-Parkinson drug, rasagiline
by
Youdim MB, Weinstock M.
Technion-Faculty of Medicine,
Eve Topf and NPF Centers,
31096, Haifa, Israel.
youdim@tx.technion.ac.il
Mech Ageing Dev. 2002 Apr 30;123(8):1081-6.


ABSTRACT

A number of studies have shown that the selective monoamine oxidase (MAO)-B inhibitor l-selegiline has neuroprotective activities in several cell culture systems and in vivo. The suggestion has been made that the propargyl moiety in this molecule may have some intrinsic neuroprotective activity not related to its ability to bind covalently to MAO B and inhibit it. We have therefore developed a number of novel drugs based on rasagiline (N-propargyl-1R-(+)-aminoindan), a potent anti-Parkinson-propargyl-containing MAO-B inhibitor drug with structural resemblance to selegiline, for the treatment of Alzheimer's disease. These drugs possess a carbamate moiety for cholinesterase (ChE), and a propargyl group for MAO inhibition. The R-enantiomer of these compounds (TV3326) has ChE and MAO inhibitory activities in vivo and retains the neuroprotective properties of rasagiline. It also exhibits anti-depressant activity in animal models. The S-enantiomer does not inhibit MAO and has no anti-depressant activity, but it has similar ChE inhibitory and neuroprotective activities. Thus MAO inhibition by propargylamines is not a pre-requisite for neuroprotection. Rather, propargylamines have some intrinsic neuroprotective property whose mechanism of action requires further elucidation.


MAOIs
Rasagiline
Neuroprotection
Rasagiline: structure
MAO-b inhibitors/PD
Anti-apoptotic activity
Molecular mechanisms
Rasagiline pharmacology
Induction of pro-survival genes
Rasagiline and the mitochondria
Antioxidant strategies against aging
Anti-Alzheimer/anti-Parkinson's drugs
Rasagiline versus selegiline metabolites
Rasagiline/ anti-apoptotic bcl-2 gene family
Dual AChE and MAO inhibitors and Alzheimer's
Rasagiline v selegiline: neuronal survival effects
Rasagiline (Agilect) in early Parkinson's disease
From rasagiline (Azilect) to ladostigil and the M30 HLA-20 series


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