Classification and bioavailability studies with WE 941 by quantitative pharmaco-EEG and clinical analyses.
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.
D000328:Adult; D001381:Azepines / Q000378:metabolism / Q000494:pharmacology*; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004569:Electroencephalography; D005260:Female; D005479:Flurazepam / Q000494:pharmacology; D006801:Humans; D006993:Hypnotics and Sedatives / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D010919:Placebos; D013997:Time Factors; D014230:Triazoles / Q000378:metabolism / Q000494:pharmacology*
D001381:Azepines; D006993:Hypnotics and Sedatives; D010919:Placebos; D014230:Triazoles; D005479:Flurazepam