Reversal of cognitive impairment by heptyl physostigmine, a long-lasting cholinesterase inhibitor, in primates

• Published in: Journal of the neurological sciences Vol. 107; no. 2; p. 246
• Main Authors: Rupniak, N M, Tye, S J, Brazell, C, Heald, A, Iversen, S D, Pagella, P G
• Format: Journal Article
• Language: English
• Published: Netherlands 01-02-1992
• Subjects: Acetylcholinesterase - blood; Analysis of Variance; Animals; Body Temperature Regulation - drug effects; Cholinesterase Inhibitors - pharmacology; Cognition - drug effects; Dose-Response Relationship, Drug; Erythrocyte Membrane - enzymology; Macaca mulatta; Male; Memory - drug effects; Physostigmine - analogs & derivatives; Physostigmine - pharmacology; Reference Values; Saimiri; Scopolamine - pharmacology; Time Factors
• ISSN: 0022-510X
• DOI: 10.1016/0022-510X(92)90296-W

Cholinergic replacement therapy for Alzheimer's disease using existing cholinesterase inhibitors is compromised by short duration, meagre benefits restricted to subgroups of patients, and peripheral toxicity. Heptyl physostigmine is a lipophilic carbamate derivative of physostigmine. In rhesus monkeys, heptyl physostigmine (0.2-0.9 mg/kg i.m.) fully reversed a scopolamine-induced cognitive impairment. Following oral administration in squirrel monkeys, heptyl physostigmine (8 mg/kg) induced long-lasting hypothermia (greater than or equal to 4 h), a centrally-mediated cholinergic effect. Erythrocyte acetylcholinesterase activity was inhibited by 86% at the time of peak hypothermia (180 min). Clinical trials with heptyl physostigmine will enable a more rigorous evaluation of cholinomimetic therapy for dementia.