Dimebon (
latrepirdine) was developed and used in Russia as an over-the-counter oral
antihistamine for
allergy treatment. In the early 1990s,
Dimebon was characterized as a low-affinity
NMDA receptor antagonist by Dr. Sergey Bachurin and his colleagues. An initial small-scale, open-label trial of
Dimebon in 14
Alzheimer's disease (AD) patients demonstrated potential efficacy.
Dimebon was then patented for the treatment of
neurodegenerative disorders and licensed by Medivation. Extremely promising results were obtained in a double-blind, placebo-controlled, phase II AD trial in 183 patients; however, a phase II trial of
Dimebon in 91
Huntington's disease patients was much less successful. Recently, a phase III AD trial of
Dimebon in 598 patients failed to result in any significant improvement in primary or secondary outcomes. The failure of
Dimebon may be in large part due to insufficient understanding of its mechanism of action. The
NMDA receptor blocking activity of
Dimebon is too weak to be physiologically relevant, while the proposed "novel mitochondrial mechanism of action" lacks credible scientific evidence or a molecular target. Independent studies indicate that the clinical effects of
Dimebon most likely result from inhibition of
histamine H₁ and
serotonin 5-HT₆ receptors. Careful preclinical studies of novel potential
therapies are needed to minimize chances of making similar costly mistakes in the future.