When applied centrally to animals, growth hormone-releasing hormone (GHRH) stimulates slow-wave sleep (SWS), whereas somatostatin (SRIF) increases REM sleep. We investigated whether these peptides also affect the sleep EEG in humans when given intravenously by comparing polysomnographically the effects of four boluses of (1) placebo, (2) 50 µg GHRH or (3) 50 µg SRIF administered at 22.00, 23.00, 24.00 and 1.00 h to 7 male controls. In addition, we collected blood samples through a long catheter every 20 min from 22.00 to 7.00 h and measured plasma cortisol and growth hormone (GH) levels. In comparison with SRIF and placebo, GHRH produced a significant increase in plasma GH concentration throughout the night (mean ± SD: 10.8 ± 2.0 ng/ml after GHRH; 3.0 ± 1.7 ng/ml after SRIF and 3.2 ± 2.0 ng/ml after placebo). SRIF failed to substantially attenuate the nocturnal GH release. Nocturnal cortisol secretion was blunted after GHRH but remained unaffected by SRIF (61.4 ± 12.9 ng/ml after placebo; 46.6 ± 19.7 ng/ml after GHRH and 70.8 ± 12.6 ng/ml after SRIF). Quantitative sleep EEG staging showed a significant increase in SWS after GHRH administration but no change after SRIF (percent spent in SWS per night: 14.0 ± 5.6 after placebo, 20.2 ± 6.6 after GHRH and 15.1 ± 8.2 after SRIF). Application of SRIF was accompanied by a trend toward increased REM density. The effects of episodic GHRH administration upon SWS, GH and cortisol secretion were opposite to those previously reported for corticotropin-releasing hormone, which supports the view that neuroregulation of human sleep involves an interaction of central GHRH and corticotropin-releasing hormone.
Pharmacokinetic measurements, neuroendocrine responses, and side effects profiles of intravenous infusions of 20 mg citalopram over 30 minutes during the early afternoon have been studied. Eight healthy male volunteers were enrolled in a placebo- (saline) controlled, single-blind, cross-over protocol. Plasma concentrations of the parent compound showed a double exponential decay. Demethyl and didemethyl metabolites were not detectable, but low concentrations of the propionic acid derivative of citalopram were found. Determination of the citalopram enantiomers yielded a balanced S(+)/R(-) ratio of 0.9 to 1.2. The endocrine response to the drug was characterized by significant increases in plasma prolactin and cortisol. Except for one subject, who developed pronounced side effects, human growth hormone showed a surge following saline that was inhibited following citalopram. Rectal temperature and heart rate were not affected and tolerability was favorable. Because of citalopram's extremely high selectivity for the presynaptic 5-hydroxytryptamine 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.
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