Bibliographic
Dimebon, a non-selective antihistamine, has recently emerged as a potential treatment for Alzheimer's disease. Dimebon has been reported to rescue cultured neurons from the neurotoxic effects of amyloid-beta and, improve learning in an active avoidance task in a rat model of AD, where cholinergic transmission is depleted by the neurotoxin AF64A. The mechanism underlying this activity is unknown though it has been suggested that it may be associated with its anti-cholinergic action. However, confounding this interpretation are data indicating that dimebon exerts other potentially cognitive enhancing activities including: antagonism of 5HT6, 5HT2c, 5HT5a receptors, α-adrenergic receptors and an inhibitory effect on NMDA receptors. Dimebon has also been reported to be neuroprotective, and to have anti-neuroinflammatory activity. The goal of this study was to examine the effect of treating aged and young rats with dimebon for 7 days and to evaluate any potential effect on the well-described age-related glial activation. The data indicate that dimebon failed to modulate the age-related deficit in learning in the Morris water maze, and the age-related increase in expression of markers of activation of microglia and astrocytes. Based on these results the authors concluded that, despite its cognitive enhancing effects in some models, dimebon failed to modulate the deficit in spatial learning in aged rats and the evidence suggests that the drug does not possess anti-inflammatory properties.