Dimebon, launched earlier in Russia as an
antihistamine drug, was evaluated as a representative of a new generation of anti-Alzheimer's drugs that have two beneficial actions: (1) to alleviate symptoms, and (2) to prevent progression of the disease. The
drug demonstrated cognition and memory-enhancing properties in the active avoidance test in rats treated with the
neurotoxin AF64A, which selectively destroys cholinergic neurons.
Dimebon protected neurons in the cerebellum cell culture against the neurotoxic action of
beta-amyloid fragment (A beta 25-35, EC50 = 25 microM). In vitro,
Dimebon displayed Ca(2+)-blocking properties (IC50 = 57 microM, on isolated rat ileum intestine) and pronounced
anticholinesterase activity (IC50 = 7.9 microM and 42 microM for
butyrylcholine esterase and
acetylcholine esterase, respectively). It also exhibited strong anti-
NMDA activity in the prevention of
NMDA-induced
seizures in mice (EC50 = 42 +/- 6 mg/kg i.p.). A beneficial effect of
Dimebon in the
therapy of
Alzheimer's disease was demonstrated in a pilot clinical trial performed in the Moscow Center of Gerontology. Fourteen patients who participated in the trial were evaluated for their state of personality and for the severity of the disease. The evaluation included orientation (space, place, time, and patient personality), memory for the past and present, life in present, speech, irritability, and so forth. During and after the eight-week
therapy with
Dimebon, cognitive and self-service functions of patients improved significantly, and psychopathic symptoms, anxiety, depression, tearfulness, and
headache were substantially diminished. The results of these studies suggest
Dimebon as a new candidate for the
therapy of Alzheimer's-like disorders.