Psychoactivity, pharmacodynamic properties and drug tolerance of 2-bromo-4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f]1,2-(4-triazolo)[4,3-a][1,4]diazepine (
WE 941), a new
triazolodiazepine, were studied in 10 normal subjects utilizing quantitative pharmaco-EEG and clinical evaluation methods. In the double-blind, placebo-controlled trial, the subjects received randomized at weekly intervals oral single doses of 0.1 mg, 0.3 mg and 0.5 mg
WE 941, placebo, and 30 mg
flurazepam as reference substance. Measurements were obtained before and at the 2nd, 4th, 6th h post
drug. EEG power spectral density analysis demonstrated no changes after placebo, while
WE 941 and
flurazepam induced statistically significant alterations characterized by an increase in beta-activity, a decrease in alpha-activity and increase in average frequency ("
anxiolytic pharmaco-EEG profile"). In addition, 0.3 mg and 0.5 mg
WE 941 and 30 mg
flurazepam produced a significant augmentation of delta-activity indicating
hypnotic qualities. Considering spontaneous and placebo-induced alterations, evaluation of the time- and dose-effect relationship indicated that all active substances exerted a
tranquilizing effect throughout 8 h, while the
hypnotic properties of 0.1 mg
WE 941 were minimal (up to the 4th h), those of 0.3 mg
WE 941 were moderate (up to 6 h) and those of 0.5 mg
WE 941 were marked (up to 8 h). The dosage equipotent to 30 mg
flurazepam is 0.3 mg
WE 941. Heart rate and blood pressure exhibited no relevant changes, while side effects including
fatigue, drowsiness and
dizziness were mostly observed after the highest dosage of
WE 941.