Analysis of the specificity of physostigmine stimulation of adrenocorticotropin in man.

Abstract

Five normal men were given infusions of saline and three doses (6, 12, and 18 micrograms/kg) of physostigmine, a centrally acting anticholinesterase, after pretreatment with glycopyrrolate, a peripheral cholinergic antagonist. There was no increase in basal ACTH or cortisol concentrations in any of the subjects after saline or the two smaller doses of physostigmine. However, each subject had a marked increase in ACTH and cortisol levels after the largest dose of physostigmine. These changes were preceded in each subject by the occurrence of noxious side effects and were accompanied by a rise in PRL levels in four of the subjects. Four subjects who received physostigmine (12 micrograms/kg) without glycopyrrolate pretreatment also experienced noxious side effects; these symptoms were followed by elevations in ACTH, cortisol, and PRL levels. These findings suggest that physostigmine stimulates ACTH and cortisol secretion through a stress-mediated effect rather than through a specific cholinergic mechanism. Consequently, physostigmine is not a reliable tool for investigating the cholinergic regulation of ACTH and cortisol.