Heat loss, sleepiness, and impaired performance after diazepam administration in humans

Abstract

In spite ofthe accumulation of knowledge regardingtheneuropharmacologicalaction of benzodiazepines (Bz), thephysiologicalprocess by which their sedative/hypnotic effects are induced remains poorly understood. We conducted a single-blind, crossovertrialto evaluatethe 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 oraldose of either5 or 10mg of DZP or placebo 12h after his average sleep onset time. Changes in plasma DZP concentration, proximalbodytemperature (p-BT), distalbody temperature (d-BT), subjective sleepiness measured bytheVisualAnalog Scale and Stanford SleepinessScale, and psychomotor performance measured by Choice Reaction Time were monitored under a modified constant routine conditionin which various factors affecting thermoregulation, alertness, and psychomotor performances were strictly controlled. Orallyadministered DZP induced a significant transient decrease in p-BT and psychomotor performance as wellas an increase in d-BT andsubjective sleepiness. Distal—p-BT gradient (DPG; difference between d-BT and p-BT), which is an indicator of blood flow in distal skinregions, showed a strong positive correlation with the plasma DZP concentration, indicating that DZP in clinicaldoses promotes heatloss in a dose-dependent manner. The DPG also correlated positively with the magnitude of subjective sleepiness and impairedpsychomotor performance. These findings indicate that the sedative/hypnotic effects of Bz could be due, at least in part, to changes inthermoregulation, especially in the process of heat loss, in humans. © 2003 Nature Publishing Group.