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Electrophysiological aspects of benzodiazepine antagonists, Ro 15‐1788 and Ro 15‐3505.
Author(s) -
Gath I,
Weidenfeld J,
Collins GI,
Hadad H
Publication year - 1984
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1984.tb02502.x
Subject(s) - midazolam , electroencephalography , benzodiazepine , placebo , electrophysiology , hypnotic , anesthesia , medicine , pharmacology , receptor , pathology , alternative medicine , psychiatry , sedation
The comparative action of two specific benzodiazepine antagonists, Ro 15‐1788 and Ro 15‐3505 was examined in six healthy volunteers. Medication was given i.v. in a double‐blind cross over pattern, and EEG was recorded throughout each experimental session. Ten minutes 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. It has been found that 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 it has been found that Ro 15‐3505 was at least 4‐5 times more potent than Ro 15‐1788.