Changes in Averaged Photopalpebral Reflex in Man by A New Benzodiazepine Derivative

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Abstract
The authors have predicted the clinical effects of some anxiolytic drugs by analyses of changes in the averaged photopalpebral reflex (PPR) observed in healthy human adults administered these drugs. In the present study, effects of a new benzodiazepine derivative, ID-622, which possess a potent antagonistic action to pentetrazol-induced convulsions in mice, on PPR were investigated in 8 normal male subjects aged 32-45 years. One mg and 2mg of ID-662, 5 mg of diazepam and inert placebo were given to the subject 30 min after the lunch in a double-blind, cross-over design. PPR was recorded bipolarly from the electrodes placed on the right upper and lower palpebrae before and 0.5, 1, 1.5, 2, 3, 4 hr after drug ad-ministration. Two latencies, i. e., P1 and P2 latencies, and the amplitude of PPR were measured. They were also requested to fulfil the questionnaire for self-as-sessments of drug effects. Diazepam 5mg, ID-622 1mg and 2mg statistically significantly prolonged both the latencies as compared with placebo but failed to exhibit the significant alteration on the amplitude. Statistically significant pro-longations of P1 and P2 latencies were observed by diazepam 5 mg as compared with both doses of ID-622. All the subjective symptoms were slight, however, among them the drowsiness and vagueness induced by diazepam 5 mg were rela- tively potent. These results suggest that ID-622 possess an anxiolytic action, however, 5 mg of diazepam seems to be more potent than the used doses of ID-622 and it is considered to be not always suitable to determine the equipotent dose based on the anti-pentetrazol action in mice alone.

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