NEUROENDOCRINE EFFECTS OF A 20-MG CITALOPRAM INFUSION IN HEALTHY-MALES - A PLACEBO-CONTROLLED EVALUATION OF CITALOPRAM AS 5-HT FUNCTION PROBE

Pharmacokinetic measurements, neuroendocrine responses, and side effec t profiles of intravenous infusions of 20 mg citalopram over 30 minute s during the early afternoon have been studied. Eight healthy male vol unteers were enrolled in a placebo- (saline) controlled, single-blind, cross-over protocol. Plasma concentrations of the parent compound sho wed a double exponential decay. Demethyl and didemethyl metabolites we re not detectable, but low concentrations of the propionic acid deriva tive of citalopram were found. Determination of the citalopram enantio ners yielded a balanced S(+)/R(-) ratio of 0.9 to 1.2. The endocrine r esponsed to the drug was characterized by significant increases in pla sma prolactin and cortisol. Except for one subject, who developed pron ounced side effects, human growth hormone showed a surge following sal ine that was inhibited following citalopram. Rectal temperature and he art rate were not affected and tolerability was favorable. Because of citalopram's extremely high selectivity for the presynaptic 5-hydroxyt ryptamine nerve terminals, the present data suggest that it might be a promising tool for the investigation of serotonergic function in the human brain in vivo.