On the distribution of REM and NREM sleep under two benzodiazepines with comparable receptor affinity but different kinetic properties.
Two clinical-pharmacological investigations were performed to give a retrospective and explorative record, based on electroencephalographic parameters, of spindle density and REM distribution in the first and second halves of the night under a short-acting (triazolam) and medium-acting (lormetazepam) benzodiazepine. A further aim was to determine whether a suitable dose of a short-acting benzodiazepine could lead to a REM suppression in the first sleep cycles and a REM compensation in later sleep cycles on the same night. Since sleep spindles are increased and rapid eye movements reduced under benzodiazepines, the two phenomena were respectively taken as indicators of drug effects on NREM and REM sleep. According to the receptor affinity of the two substances, dosages of triazolam and lormetazepam ought to be equieffective in a ratio of about 1:2. Yet clinical experience has shown that a ratio of 1:4 (0.5 mg triazolam vs. 2 mg lormetazepam) gives the doses that are equieffective and which are widely used in clinical practice. The changes in the number of sleep spindles and rapid eye movements documented the different kinetic properties of the two substances. Even after clinically equieffective doses, the changes in the parameters were less marked under lormetazepam than under triazolam. This suggests that the two benzodiazepines different effects on spindle and REM distribution were not attributable to their kinetics, but that pharmacodynamic aspects must also be considered, even if this does not fit in with the prevalent picture of the benzodiazepines mechanisms of action.(ABSTRACT TRUNCATED AT 250 WORDS)
D000293:Adolescent; D000328:Adult; D014151:Anti-Anxiety Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001569:Benzodiazepines; D004311:Double-Blind Method; D004569:Electroencephalography; D005260:Female; D006801:Humans; D008140:Lorazepam / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011897:Random Allocation; D011963:Receptors, GABA-A / Q000378:metabolism; D012189:Retrospective Studies; D012894:Sleep Stages / Q000187:drug effects*; D012895:Sleep, REM / Q000187:drug effects; D014229:Triazolam / Q000493:pharmacokinetics / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D014229:Triazolam; C023842:lormetazepam; D008140:Lorazepam