title: Alterations to plasma melatonin and cortisol after evening alprazolam administration in humans.
abstract: Six healthy volunteers were given a 2-mg dose of alprazolam at 21:00 h and hourly blood samples were collected until 08:00 h the following morning. A control night of hourly blood sampling was undertaken 7 days before Plasma was analyzed for melatonin, cortisol, and alprazolam concentrations. Melatonin concentrations were significantly suppressed by alprazolam at 23:00, midnight, 01:00, 06:00, and 07:00 h. A trend toward suppression was evident from 02:00 to 05:00 h. Cortisol concentrations were also suppressed by alprazolam at several times throughout the night (01:00-04:00 h). Plasma alprazolam levels showed a peak at 3 h and remained relatively high 19-20 h after the dose. The significance of melatonin suppression by alprazolam is discussed in terms of benzodiazepine binding sites and GABA minergic transmission in the human pineal gland, suprachiasmatic nuclei, and retina. Plasma cortisol suppression has been reported for other benzodiazepine drugs, but conflicting data exist for alprazolam. The present results do not support the proposed inhibitory effect of melatonin on the hypothalamic-pituitary-adrenal (HPA)-axis. It is suggested that there is no simple direct relationship between melatonin and the HPA axis in humans.
authors.affiliation: Victorian Institute of Forensic Pathology, Monash University, South Melbourne, Australia.
authors.forename: I M
authors.initials: IM
authors.lastname: McIntyre
authors.forename: T R
authors.initials: TR
authors.lastname: Norman
authors.forename: G D
authors.initials: GD
authors.lastname: Burrows
authors.forename: S M
authors.initials: SM
authors.lastname: Armstrong
mesh_terms: D000328:Adult; D000525:Alprazolam / Q000008:administration & dosage / Q000494:pharmacology*; D002940:Circadian Rhythm / Q000187:drug effects*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D008550:Melatonin / Q000097:blood*; D015999:Multivariate Analysis
chemical_list: D008550:Melatonin; D006854:Hydrocortisone; D000525:Alprazolam