EFFECTS OF THE ACETYLCHOLINESTERASE INHIBITOR ENA-713 ON ISCHEMIA-INDUCED CHANGES IN ACETYLCHOLINE AND AROMATIC AMINE LEVELS IN THE GERBIL BRAIN

The effects of a new acetylcholinesterase inhibitor, ENA-713, on ische mia-induced changes in acetylcholine, monoamines, and their metabolite s, were studied in the gerbil. ENA-713 (0.2 mg/kg) or saline was admin istered intraperitoneally to gerbils 30 min before induction of cerebr al ischemia by bilateral carotid occlusion. Pretreatment with ENA-713 mitigated the ischemia-induced abnormalities of the cholinergic, dopam inergic and serotoninergic systems in the gerbil brain, although it ha d virtually no effect on acetylcholine, monoamines, or their metabolit es in any region of the normal gerbil brain. These findings suggest th at ENA-713 has beneficial effects against ischemia-induced cerebral di sorders. Thus, ENA-713 seems to be promising as a preventive or therap eutic agent for cerebrovascular dementia due to cerebral ischemia and might be useful for the treatment of Alzheimer-type dementia which is associated with multiple neurotransmitter abnormalities in the brain.