Selegiline for Alzheimer’s disease

Department of Clinical Geratology, University of Oxford, Oxford, UK, OX2 6HE.
Cochrane database of systematic reviews (Online) (Impact Factor: 6.03). 01/2003; 1(1):CD000442. DOI: 10.1002/14651858.CD000442
Source: PubMed


Despite its initial promise, i.e. the potential neuroprotective properties, and its role in the treatment of Parkinson's disease, selegiline for Alzheimer's disease has proved disappointing. Although there is no evidence of a significant adverse event profile, there is also no evidence of a clinically meaningful benefit for people with Alzheimer's disease. There would seem to be no justification, therefore, to use it for Alzheimer's disease, nor for any further studies of its efficacy in Alzheimer's disease.

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    • "In patients with moderate impairment from AD, treatment with selegiline slowed the progression of disease (Sano et al 1997; Filip and Colibas 1999; Knoll 2003). However, according to recent data from a meta-analysis, selegiline significantly improved cognition and activities of daily living at an earlier time point, but not at a later assessment time (Wilcock et al 2002; Birks and Flicher 2003). Selegiline prevents the effects of oxidative stress in a variety of models both in vitro and in vivo (Youdim et al 2001). "
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    ABSTRACT: We investigated the effects of rivastigmine (a cholinesterase inhibitor) and selegiline ((-)deprenyl, an irreversible inhibitor of monoamineoxidase-B), alone and in combination, on brain acetylcholinesterase (AChE), (Na(+), K(+))-, Mg(2+)-ATPase activities, total antioxidant status (TAS), and learning performance, after long-term drug administration in aged male rats. The possible relationship between the biochemical and behavioral parameters was evaluated. Aged rats were treated (for 36 days) with rivastigmine (0.3 mg/kg rat/day ip), selegiline (0.25 mg/kg rat/day im), rivastigmine plus selegiline in the same doses and way of administration as separately. Aged and adult control groups received NaCl 0.9% 0.5 ml ip. TAS was lower in aged than in adult rats, rivastigmine alone does not affect TAS, decreases AChE activity, increases (Na(+), K(+))-ATPase and Mg(2+)-ATPase activity of aged rat brain and improves cognitive performance. Selegiline alone decreases free radical production and increases AChE activity and (Na(+), K(+))-ATPase activity, improving cognitive performance as well. In the combination: rivastigmine seems to cancel selegiline action on TAS and AChE activity, while it has additive effect on (Na(+), K(+))-ATPase activity. In the case of Mg(2+)-ATPase selegiline appears to attenuate rivastigmine activity. No statistically significant difference was observed in the cognitive performance. Reduced TAS, AChE activity and learning performance was observed in old rats. Both rivastigmine and selesiline alone improved performance, although they influenced the biochemical parameters in a different way. The combination of the two drugs did not affect learning performance.
    Neuropsychiatric Disease and Treatment 09/2008; 4(4):687-99. · 1.74 Impact Factor
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    • "1a and 2b). This was based on the clinical findings that ChE inhibitors like rivastigmine and donepezil have cognitive enhancing effects under this condition (Weinstock et al., 2000a,b), while the MAO B inhibitor, selegiline, delays its progression in some subjects (Birks and Flicker, 2000). Furthermore , we reasoned that these compounds might well have a neuroprotective action similar to that of rasagiline (Table 1). "
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    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.
    Mechanisms of Ageing and Development 05/2002; 123(8):1081-6. DOI:10.1016/S0047-6374(01)00391-8 · 3.40 Impact Factor
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    ABSTRACT: eeks to prevent, delay or palliate the appearance of the symptoms indicating an alteration in the levels of neurotransmitters, and i ts chief objective is to maintain them. Pharmacology has already provided neurologists with a wide range of tried and tested drugs, yet the results obtained in research laboratories in the last few years seem to indicate that the number of therapeutic possibiliti es are very likely to rise sharply in the future. Progress made in genomics and the better understanding of cellular biochemical cycle s allow us to expect that this century will finally be that of the Neurosciences, and that Neurology, without losing its cognitive esse nce, will start to be considered to be a speciality that is as therapeutic as it is diagnostic. (REV NEUROL 2003; 36: 1047-57)
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