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Electrophysiological aspects of benzodiazepine antagonists ro 15 1788 flumazepil and ro 15 3505 ethyl 7 chloro 5 6 dihydro 5 methyl 6 oxo 4h imidazo 1 5 a 1 4 benzodiazepine 3 carboxylate


, : Electrophysiological aspects of benzodiazepine antagonists ro 15 1788 flumazepil and ro 15 3505 ethyl 7 chloro 5 6 dihydro 5 methyl 6 oxo 4h imidazo 1 5 a 1 4 benzodiazepine 3 carboxylate. British Journal of Clinical Pharmacology 18(4): 541-548

The comparative action of 2 specific benzodiazepine antagonists, Ro 15-1788 and Ro 15-3505, was examined in 6 healthy volunteers. Medication was given i.v. in a double-blind cross over pattern, and EEG was recorded throughout each experimental session. Ten min after the injection of one of the antagonists or placebo, midazolam was injected in incremental doses until first signs of drowsiness appeared in the EEG. The EEG was computer analyzed, using adaptive segmentation and time-dependent clustering. Continuous power profiles for various frequency bands, as well as power ratios for the physiological frequency bands (e.g., sigma/alpha power ratio) were generated. Sigma/alpha power ratio was the most sensitive parameter detecting early effects of midazolam on the EEG signal, thus enabling a semi-quantitative titration of the antagonists by midazolam. Ro 15-1788 in doses of 5 mg i.v. was counteracted on average by 7.3 mg midazolam. From the EEG analysis, Ro 15-3505 was at least 4-5 times more potent than Ro 15-1788. [Such selective benzodiazepine antagonists have a highly potential use in controllability of anesthesia and the post-operative period, and as antidotes in cases of overdosage of benzodiazepines.].

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