The influence of the muscarinic agonist RS 86 on the cortisol system.

To test the assumption that activation of the hypothalamic-pituitary-adrenocortical (HPA) axis is mediated by cholinergic neurons, the cortisol response to the administration of the muscarinic agonist RS 86 was investigated in 12 healthy volunteers. In addition, prolactin and growth hormone secretion patterns were assessed. No significant increase in plasma cortisol or growth hormone was observed after the administration of 1.5 and 3.0 mg RS 86, respectively. However, there was a slight increase in prolactin serum concentration after 3.0 mg RS 86. As RS 86, when used in the same dose range, causes a shortening of rapid eye movement (REM) latency and displays antimanic properties, it is unlikely that a reduced dosage of RS 86 in itself accounts for the lack of stimulation of the HPA axis. If one assumes that in humans the stimulation of the HPA axis is under cholinergic control, then the failure of RS 86 to increase cortisol might be attributable to the fact that different subtypes of muscarinic neurons, for which RS 86 is not a full agonist, are involved, or else nicotinic neurons are implicated in the activation of the HPA axis.