Latrepirdine

Latrepirdine (INN, also known as dimebolin and sold as Dimebon), is an antihistamine drug which has been used clinically in Russia since 1983.

Research is continuing in both Russia and western nations into potential applications as a neuroprotective drug to combat Alzheimer's disease and, possibly, as a nootropic as well. However, a Phase III clinical trial for Alzheimer's disease (AD) treatment failed to show any benefit. Three other AD trials continue. Dimebon failed in the phase III trial for Huntington disease.

Uses
Latrepirdine is an orally-active small molecule compound that has been shown to inhibit brain cell death in preclinical studies of Alzheimer's disease and Huntington's disease, making it a potential treatment for these and other neurodegenerative diseases. Research suggests that it may also have cognition-enhancing effects in healthy individuals, in the absence of neurodegenerative disease pathology.

Alzheimer's disease: failed clinical trial
Latrepirdine attracted renewed interest in 2009 after being shown in small preclinical trials to have positive effects on persons suffering from Alzheimer’s disease. Animal studies showing potential beneficial effects on Alzheimer's disease models were shown in Russian research in 2000. Preliminary results from human trials have also been promising. In an initial six-month phase II trial, results have shown that at 12 months there was significant improvement over placebo. Latrepirdine showed promising results in a Phase III equivalent double blind trial in Russia with mild–moderate stage patients. In April 2009, Pfizer and Medivation initiate a phase III trial (CONCERT study) aiming for FDA approval. In March 2010, Pfizer announced that this clinical trial failed to show any benefit for the treatment of Alzheimer's disease patients.

Numerous phase III trials for AD were recruiting in 2009.

In July 2009 Pfizer and Medivation announced that latrepirdine will be the proposed international nonproprietary name for latrepirdine for the treatment of Alzheimer's.

In March 2010 the results of a clinical trial phase III were released. It was announced that the investigational Alzheimer's disease drug dimebon failed in the pivotal CONNECTION trial of patients with mild-to-moderate disease.

Huntington's disease
In April 2011 latrepirdine failed in a Phase 3 clinical trial of patients affected with Huntington’s disease. The trial was sponsored by Medivation Inc. and Pfizer.

Pharmacology
Latrepirdine appears to operate through multiple mechanisms of action, both blocking the action of neurotoxic beta-amyloid proteins and inhibiting L-type calcium channels, modulating the action of AMPA and NMDA glutamate receptors, and may exert a neuroprotective effect by blocking a novel target that involves mitochondrial pores, which are believed to play a role in the cell death that is associated with neurodegenerative diseases and the aging process. It also blocks a number of other receptors including α-adrenergic, 5-HT2C, 5-HT5A, and 5-HT6. It is of significance to note that latrepirdine lacks any anticholinergic effects.