Nocturnal psychometric assessment of the hypnotic activity of low and normal doses of brotizolam.
The hypnotic activity of acute doses of 0.125 mg and 0.250 mg brotizolam (CAS 57801-81-7, Lendormin) was compared in a double-blind randomised placebo-controlled study. Forty-nine healthy female volunteers aged between 23 and 44 years were enrolled. Trial medication was administered sublingually at 9:15 p.m. and 9:30 p.m., respectively. The nocturnal investigations continued until 2:30 a.m. A final examination was performed in the morning after breakfast. Every 30 min mood was measured by visual analogue scales. A computerised psychometric test (CDT) over 8 min was undertaken in order to measure continuous attention under short-term memory load. The Digit Symbol Substitution Test (DSST) was performed every hour. The CDT was not evaluable due to significant baseline differences. A statistically significant sedative effect in the DSST was already found 30 min after administration of 0.250 mg brotizolam, while the effect of 0.125 mg brotizolam just failed to reach the threshold of significance. Both treatments showed equivalent efficacy at 0.5, 1.5 and 2.5 h after administration. After 3.5 and 4.5 h there was no statistically significant difference between placebo and 0.125 mg brotizolam. After 4.5 h 0.250 mg brotizolam still showed significant hypnotic activity compared to placebo and 0.125 mg brotizolam. No treatment effects on mood were apparent according to the visual analogue scales. Furthermore, no hangover effects were detected for any of the parameters measured. The pharmacodynamic results confirmed the duration of action of more than 4.5 of h 0.250 mg brotizolam found in earlier studies and suggest that 0.125 mg is as effective as 0.250 mg with regard to sleep onset disturbances but has a shorter duration of action.
Leonard
J P
JP
Boehringer Ingelheim KG, Clinical Research Ingelheim, Ingelheim/Rhein, Germany.
Heinrich-Nols
J
J
Roth
T G
TG
D000328:Adult; D000339:Affect / Q000187:drug effects; D001381:Azepines / Q000494:pharmacology*; D002110:Caffeine / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004311:Double-Blind Method; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008875:Middle Aged; D011594:Psychometrics; D013805:Theobromine / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D001381:Azepines; D002492:Central Nervous System Depressants; D000697:Central Nervous System Stimulants; D006993:Hypnotics and Sedatives; D014665:Vasodilator Agents; D002110:Caffeine; D000431:Ethanol; C020960:brotizolam; D013805:Theobromine