Antagonistic Effects of Physostigmine and Methylphenidate in Man

The authors describe the antagonistic effects of physostigmine, a centrally acting acetylcholinesterase inhibitor, and methylphenidate, an amphetamine-like stimulant, on manic and schizophrenic patients. In both patient groups, physostigmine increased behavioral inhibition and decreased behavioral activation; patients displayed symptoms that are characteristic of psychomotor inhibition. Methylphenidate had the opposite effect of increasing activation and decreasing inhibition. Treatment with each drug antagonized the effects of the other. In the schizophrenic patients, physostigmine prevented and reversed the meththylphenidate-induced symptoms of psychosis. In manic patients, physostigmine decreased and methylphenidate increased manic symptoms.