Classification and assessment of cerebral bioavailability of lopirazepam (D-12524) by quantitative EEG and psychometric analysis.
In this double-blind, placebo-controlled study the CNS efficacy and pharmacodynamic properties of 3-hydroxy-5-(o-chlorophenyl)-7-chloro-1,2-dihydro-3H-pyrido[3,2-e]-1,4-diazepin-2-one (lopirazepam, D-12524) was investigated in a group of 10 normal volunteers. Quantitative EEG and psychometric analyses and clinical evaluations were done before as well as 2, 4, 6 and 8 h after oral administration of single doses of placebo, 3 mg, 5 mg and 10 mg lopirazepam and 10 mg prazepam. EEG digital computer period analysis demonstrated dose-dependent changes which are typical of the class of anxiolytics and which started in the 2nd hour, peaked in the 4th hour and lasted after 3 mg, 5 mg and 10 mg up to the 4th, 6th and 8th hour, respectively, 10 mg D-12524 produced an additional augmentation of slow waves indicating sleep-inducing qualities in this dosage. The equipotent dosage to 10 mg prazepam seems to be 5 mg. Psychometric analyses demonstrated an improvement in attention, psychomotor performance, mood and affectivity after 3 mg, opposite changes after 10 mg D-12524. Flickerlight fusion, reaction time, after-image and EAS score were determined as well. Data concerning side effects, pulse rate and blood pressure suggested a good tolerance of the drug.
D000328:Adult; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000523:psychology; D001288:Attention / Q000187:drug effects; D001682:Biological Availability; D001921:Brain / Q000378:metabolism; D004311:Double-Blind Method; D004569:Electroencephalography; D004644:Emotions / Q000187:drug effects; D005260:Female; D005425:Flicker Fusion / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008140:Lorazepam / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D009048:Motor Skills / Q000187:drug effects; D011222:Prazepam / Q000494:pharmacology; D011594:Psychometrics; D011619:Psychotropic Drugs / Q000378:metabolism; D011930:Reaction Time / Q000187:drug effects; D013997:Time Factors
D014151:Anti-Anxiety Agents; D011619:Psychotropic Drugs; D008140:Lorazepam; D011222:Prazepam