A useful tool for predicting the clinical effects of hypnotics in humans: averaged photopalpebral reflex

The averaged photopalpebral reflex (PPR) is an index which objectively assesses the arousal level of humans. The dose-response curve of flunitrazepam, a benzodiazepine derivative, was investigated by using PPR in the present study. Ten healthy male university students were given flunitrazepam 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg and placebo in a double-blind, crossover design. PPR and subjective assessment were recorded before and after drug administration. P1 and P2 latencies of PPR were prolonged by flunitrazepam 0.5 mg, 1.0 mg and 1.5 mg in a dose-dependent manner. The prolongation of latencies by flunitrazepam 2.0 mg was weaker than that by 1.5 mg, but was more potent than that by 1.0 mg. In self-assessments, sleepiness, muscle weakness and vagueness of thought were observed after drug ingestion. Sleepiness was correlated with the prolongation of the PPR latencies. These results suggest that PPR could be a useful tool for psychopharmacological investigations in normal humans, that flunitrazepam might be a clinically potent hypnotic drug, and that its peak effect occurs 2-3 h after administration.