Attenuation of sleep propensity, core hypothermia, and peripheral heat loss after temazepam tolerance.
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 (T(ft)) and rectal (T(c)) temperatures were recorded. Sleep onset latency (SOL) was measured hourly using 20-min multiple sleep latency tests. Relative to placebo, temazepam significantly reduced both T(c) and SOL (-0.31 degrees C and 14.1 min) while increasing T(ft) (3.39 degrees 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 T(c) (-0.16 degrees C) and T(ft) (1.44 degrees C). Furthermore, SOL was temporally related to T(ft) and the maximum rate of decline in T(c) before and after tolerance. Together, these results indicate that the thermoregulatory system may be functionally involved in the regulation of sleepiness.
Gilbert
S S
SS
Centre for Sleep Research, The University of South Australia, The Queen Elizabeth Hospital, Woodville, South Australia 5011. saulg@bogfoot.com
Burgess
H J
HJ
Kennaway
D J
DJ
Dawson
D
D
D000328:Adult; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects* / Q000502:physiology; D001833:Body Temperature Regulation / Q000187:drug effects*; D004361:Drug Tolerance; D006801:Humans; D007036:Hypothermia, Induced; D008297:Male; D010919:Placebos; D012894:Sleep Stages / Q000187:drug effects* / Q000502:physiology; D016683:Supine Position; D013693:Temazepam / Q000494:pharmacology*; D013997:Time Factors
D014151:Anti-Anxiety Agents; D010919:Placebos; D013693:Temazepam