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  • Title: Cholinesterase inhibitors proposed for treating dementia in Alzheimer's disease: selectivity toward human brain acetylcholinesterase compared with butyrylcholinesterase.
    Author: Pacheco G, Palacios-Esquivel R, Moss DE.
    Journal: J Pharmacol Exp Ther; 1995 Aug; 274(2):767-70. PubMed ID: 7636741.
    Abstract:
    One consistent finding in senile dementia of the Alzheimer's type is that the brain has reduced ability to synthesize acetylcholine. This has been related, in part, to memory dysfunctions. Although a cholinergic deficit is not singularly responsible for symptoms of dementia, treatment strategies have been designed to facilitate cholinergic activity by inhibiting acetylcholinesterase (AChE). To minimize toxicity, however, a cholinesterase inhibitor selective for only AChE would be an ideal treatment. The purpose of this study was to determine the selectivity of physostigmine, metrifonate, methanesulfonyl fluoride and tetrahydroaminoacridine (tacrine) toward AChE as compared with butyrylcholinesterase (BChE) in human cortex. The results show that methanesulfonyl fluoride is selective as an inhibitor of AChE as compared with BChE. Physostigmine inhibited AChE more than BChE. Metrifonate was found to inhibit BChE more than AChE. Tetrahydroaminoacridine inhibited both enzymes in a complex way.
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