Endocrine parameters and biogenic amines in relationship to psychopathology after cholinergic drug challenge (RS-86)

The centrally active muscarinic agonist RS-86 elicited a dose-dependent anergic-anhedonic syndrome in a double-blind dose-response study in one healthy volunteer. At 4 and 5 mg, RS-86 induced escape from cortisol suppression by dexamethasone parallel to an increase in prolactin. The time course, as well as the absence of increases in plasma epinephrine and growth hormone, suggests that the changes are not due to nonspecific stress. However, there was a slight increase in plasma norepinephrine, tentatively dependent on the dose of RS-86. In 12-hour urine samples the excretion of 3-methoxy-4-hydroxy-phenylglycol and homovanillic acid tended to decrease in a dose-dependent manner, with a subsequent increase during the following nights. No systematic changes occurred in plasma dopamine, serotonin, and cyclic adenosine monophosphate or in plasma and urinary 3,4-dihydroxyphenylacetic acid or urinary vanillylmandelic acid. The findings are discussed in terms of the cholinergic-adrenergic balance hypothesis of affective disorders and biochemical findings in major depression.