CHOLINESTERASE-INHIBITORS PROPOSED FOR TREATING DEMENTIA IN ALZHEIMERS-DISEASE - SELECTIVITY TOWARD HUMAN BRAIN ACETYLCHOLINESTERASE COMPARED WITH BUTYRYLCHOLINESTERASE

One consistent finding in senile dementia of the Alzheimer's type is t hat the brain has reduced ability to synthesize acetylcholine. This ha s been related, in part, to memory dysfunctions. Although a cholinergi c deficit is not singularly responsible for symptoms of dementia, trea tment strategies have been designed to facilitate cholinergic activity by inhibiting acetylcholinesterase (AChE). To minimize toxicity, howe ver, a cholinesterase inhibitor selective for only AChE would be an id eal treatment. The purpose of this study was to determine the selectiv ity of physostigmine, metrifonate, methanesulfonyl fluoride and tetrah ydroaminoacridine (tacrine) toward AChE as compared with butyrylcholin esterase (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 en zymes in a complex way.