Attenuation of sleep propensity, core hypothermia, and peripheral heat loss after temazepam tolerance

Abstract

If changes in thermoregulation mediate sleepiness induced by sedative/hypnotics, then a reduction in the soporific efficacy (tolerance) of these agents may be accompanied by a concomitant reduction in their thermoregulatory effects. We compared the thermoregulatory and soporific effects of acute temazepam (30 mg at 1400) in 11 young male subjects before and immediately after 7 consecutive days of temazepam (30 mg). Subjects lay supine (0800–2030), while foot (Tft) and rectal (Tc) temperatures were recorded. Sleep onset latency (SOL) was measured hourly using 20-min multiple sleep latency tests. Relative to placebo, temazepam significantly reduced both Tc and SOL (−0.31°C and 14.1 min) while increasing Tft (3.39°C). A significant tolerance developed after the week of temazepam, with a mean reduction in soporific efficacy of 4.0 ± 0.8 min. This was accompanied by a concomitant attenuation in both Tc(−0.16°C) and Tft (1.44°C). Furthermore, SOL was temporally related to Tft and the maximum rate of decline in Tc before and after tolerance. Together, these results indicate that the thermoregulatory system may be functionally involved in the regulation of sleepiness.