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  • Title: Heat loss, sleepiness, and impaired performance after diazepam administration in humans.
    Author: Echizenya M, Mishima K, Satoh K, Kusanagi H, Sekine A, Ohkubo T, Shimizu T, Hishikawa Y.
    Journal: Neuropsychopharmacology; 2003 Jun; 28(6):1198-206. PubMed ID: 12700718.
    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.
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