title: Antihistamine agent Dimebon as a novel neuroprotector and a cognition enhancer.
abstract: 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.
authors.affiliation: Institute of Physiologically Active Compounds, 142432, Chernogolovka, Moscow Region, Russia.
authors.forename: S
authors.initials: S
authors.lastname: Bachurin
authors.forename: E
authors.initials: E
authors.lastname: Bukatina
authors.forename: N
authors.initials: N
authors.lastname: Lermontova
authors.forename: S
authors.initials: S
authors.lastname: Tkachenko
authors.forename: A
authors.initials: A
authors.lastname: Afanasiev
authors.forename: V
authors.initials: V
authors.lastname: Grigoriev
authors.forename: I
authors.initials: I
authors.lastname: Grigorieva
authors.forename: Y
authors.initials: Y
authors.lastname: Ivanov
authors.forename: S
authors.initials: S
authors.lastname: Sablin
authors.forename: N
authors.initials: N
authors.lastname: Zefirov
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008875:Middle Aged; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018697:Nootropic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010865:Pilot Projects; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology
chemical_list: D015220:Calcium Channels; D007211:Indoles; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D016194:Receptors, N-Methyl-D-Aspartate; C010119:latrepirdine