Classification and bioavailability studies with WE 941 by quantitative pharmaco-EEG and clinical analyses.

Area of Science:

• Pharmacology
• Neuroscience
• Psychopharmacology

Background:

• Triazolodiazepines represent a class of drugs with potential anxiolytic and hypnotic properties.
• Understanding the psychoactive and pharmacodynamic profiles of novel compounds is crucial for drug development.

Purpose of the Study:

• To evaluate the psychoactivity, pharmacodynamic properties, and drug tolerance of a new triazolodiazepine, WE 941.
• To compare the effects of WE 941 with placebo and a reference substance (flurazepam) using quantitative pharmaco-EEG and clinical evaluations.

Main Methods:

• A double-blind, placebo-controlled trial involving 10 normal subjects.
• Administration of single oral doses of WE 941 (0.1 mg, 0.3 mg, 0.5 mg), placebo, and flurazepam (30 mg).
• Quantitative pharmaco-EEG (power spectral density analysis) and clinical assessments at various time points post-drug administration.

Main Results:

• WE 941 and flurazepam induced significant EEG changes indicative of anxiolytic effects (increased beta-activity, decreased alpha-activity, increased average frequency).
• Higher doses of WE 941 (0.3 mg, 0.5 mg) and flurazepam exhibited hypnotic qualities (increased delta-activity).
• 0.3 mg WE 941 was found to be equipotent to 30 mg flurazepam, with dose-dependent tranquilizing and hypnotic effects observed for WE 941.

Conclusions:

• WE 941 possesses both anxiolytic and hypnotic properties, with a pharmacological profile similar to flurazepam.
• The study identified a therapeutic dose of 0.3 mg WE 941 as equipotent to 30 mg flurazepam.
• Observed side effects like fatigue and drowsiness were primarily associated with the highest dose of WE 941.