Preclinical study of dimebon on β-amyloid-mediated neuropathology in Alzheimer's disease
1 Department of Neurology, Mount Sinai School of Medicine, New York, New York 10029 USA
2 Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029 USA
3 Departments of Food Science and Foods&Nutrition, Purdue University, West Lafayette, Indiana 47907 USA
4 Department of Neuroscience, Mount Sinai School of Medicine, New York, New York 10029 USA
5 Geriatric Research, Education and Clinical Center, James J. Peters Veterans Affairs Medical Center, Bronx, New York 10468 USA
Molecular Neurodegeneration 2011, 6:7 doi:10.1186/1750-1326-6-7Published: 19 January 2011
Dimebon is a retired non-selective antihistamine drug currently being investigated as a therapeutic agent for the treatment of Alzheimer's disease (AD). Results from several completed clinical trials are mixed and contradictory. Proper interpretations of these clinical observations, as well as future development of dimebon in AD treatment are complicated by the lack of concrete information on the mechanisms by which dimebon might benefit AD.
The present studies are designed specifically to assess whether dimebon might modulate β-amyloid (Aβ)-mediated responses which are central to the development and progression of AD dementia. We found that dimebon is bioavailable in the brains of mice following oral administration. AD mice chronically treated with dimebon exhibited a trend of improvement in spatial memory function without affecting the levels of total Aβ as well as soluble oligomeric Aβ in the brain. The same trend of behavior improvement is also seen in wild type animals chronically treated with dimebon.
Collectively, our preclinical studies using the TgCRND8 AD mouse model demonstrated that dimebon might have some beneficial effect in improving cognitive function independent of Alzheimer's disease-type Aβ-related mechanisms or global energy metabolism in the brain. Observations from our study and others suggesting dimebon might improve cognition in wild type mice and rats raises the possibility that dimebon might be able to benefit cognitive function in patients with other neurodegenerative disorders, such as Huntington's disease, or in the aging population. Additional studies will be necessary to clarify the mechanisms by which dimebon might directly or indirectly benefit cognitive function.