title: Heat loss, sleepiness, and impaired performance after diazepam administration in humans.
abstract: In spite of the accumulation of knowledge regarding the neuropharmacological action of benzodiazepines (Bz), the physiological process by which their sedative/hypnotic effects are induced remains poorly understood. We conducted a single-blind, crossover trial to evaluate the role of the thermoregulatory process in sleepiness and impaired psychomotor performance induced by a standard Bz, diazepam (DZP). Each of the eight healthy young male volunteers (mean age, 19.75 years; range, 18-23 years) was given a single oral dose of either 5 or 10 mg of DZP or placebo 12 h after his average sleep onset time. Changes in plasma DZP concentration, proximal body temperature (p-BT), distal body temperature (d-BT), subjective sleepiness measured by the Visual Analog Scale and Stanford Sleepiness Scale, and psychomotor performance measured by Choice Reaction Time were monitored under a modified constant routine condition in which various factors affecting thermoregulation, alertness, and psychomotor performances were strictly controlled. Orally administered DZP induced a significant transient decrease in p-BT and psychomotor performance as well as an increase in d-BT and subjective sleepiness. Distal-p-BT gradient (DPG; difference between d-BT and p-BT), which is an indicator of blood flow in distal skin regions, showed a strong positive correlation with the plasma DZP concentration, indicating that DZP in clinical doses promotes heat loss in a dose-dependent manner. The DPG also correlated positively with the magnitude of subjective sleepiness and impaired psychomotor performance. These findings indicate that the sedative/hypnotic effects of Bz could be due, at least in part, to changes in thermoregulation, especially in the process of heat loss, in humans.
authors.affiliation: Department of Neuropsychiatry, Akita University School of Medicine, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Echizenya
authors.forename: Kazuo
authors.initials: K
authors.lastname: Mishima
authors.forename: Kohtoku
authors.initials: K
authors.lastname: Satoh
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kusanagi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sekine
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ohkubo
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Shimizu
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Hishikawa
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001833:Body Temperature Regulation / Q000187:drug effects* / Q000502:physiology; D003975:Diazepam / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011597:Psychomotor Performance / Q000187:drug effects* / Q000502:physiology; D012890:Sleep / Q000187:drug effects* / Q000502:physiology
chemical_list: D003975:Diazepam