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Dimebon Disappointment

Overview
Journal Alzheimers Res Ther
Date 2010 Sep 15
PMID 20836898
Citations 26
Authors
Roy W Jones
Affiliations
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Abstract

Dimebon (latrepirdine) has received widespread publicity as a potential therapy for Alzheimer's disease following a very positive phase 2 study carried out in Russia and published in the Lancet in 2008. In this study there were improvements over 6 months in all endpoints (cognitive, global, daily function and behaviour), with continuing improvement at 12 months in cognition and daily function. A more recent multinational phase 3 study, however, showed no improvements whatsoever and no difference between the two drug-treated groups and the placebo group. Of note, there was little deterioration in any of the groups after 6 months in contrast to the placebo group in the phase 2 study. The potential reasons for these disappointing results are discussed, as well as the implication for dimebon and drug treatment in Alzheimer's disease.

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References
1.
Bachurin S, Shevtsova E, Kireeva E, Oxenkrug G, Sablin S . Mitochondria as a target for neurotoxins and neuroprotective agents. Ann N Y Acad Sci. 2003; 993:334-44; discussion 345-9. DOI: 10.1111/j.1749-6632.2003.tb07541.x. View
2.
Grigorev V, Dranyi O, Bachurin S . Comparative study of action mechanisms of dimebon and memantine on AMPA- and NMDA-subtypes glutamate receptors in rat cerebral neurons. Bull Exp Biol Med. 2004; 136(5):474-7. DOI: 10.1023/b:bebm.0000017097.75818.14. View
3.
Lermontova N, Redkozubov A, Shevtsova E, Serkova T, Kireeva E, Bachurin S . Dimebon and tacrine inhibit neurotoxic action of beta-amyloid in culture and block L-type Ca(2+) channels. Bull Exp Biol Med. 2002; 132(5):1079-83. DOI: 10.1023/a:1017972709652. View
4.
Bachurin S, Bukatina E, Lermontova N, Tkachenko S, Afanasiev A, Grigoriev V . Antihistamine agent Dimebon as a novel neuroprotector and a cognition enhancer. Ann N Y Acad Sci. 2001; 939:425-35. DOI: 10.1111/j.1749-6632.2001.tb03654.x. View
5.
Doody R, Gavrilova S, Sano M, Thomas R, Aisen P, Bachurin S . Effect of dimebon on cognition, activities of daily living, behaviour, and global function in patients with mild-to-moderate Alzheimer's disease: a randomised, double-blind, placebo-controlled study. Lancet. 2008; 372(9634):207-15. DOI: 10.1016/S0140-6736(08)61074-0. View