Abstract
Prediction of the clinical effects of drugs from pharmacological findings in laboratory animals and normal human beings is a matter of importance, yet this task is especially difficult in the cases of the psychotropic drug. In the present paper, effects of some benzodiazepine derivatives on the averaged photopalpebral reflex (PPR) in man was reported. A 0.5 mg of ID-540,a new benzodiazepine derivative, prolonged latencies of PPR with a statistical significance as compared to the placebo which was administered orally to 6 healthy, male university students under a double-blind, cross-over design. The maximal prolongation of the latencies was obtained 3 hrs. after dosing. The serum concentration of ID-540 reached a peak level 2-3 hrs. after administration, while its principal metabolite, N-desmethyl-ID-540 exhibited a slow, gradual rise in serum. The latencies of PPR were positively correlated to the serum level of ID-540 but not to the N-demethylated metabolite. Two doses of prazepam, 10 mg and 20 mg, diazepam 5 mg and placebo were orally administered to 8 healthy, male university students under a double-blind, cross-over desing. Prazepam prolonged the P_1 latency depending on the doses, though the degree of prolongation of the latency after administration of prazepam 20 mg was less than that after diazepam 5 mg. The two doses of prazepma, dose-dependently, and diazepam 5 mg prolonged the P_2 latency ; however, prolongation of the latency by prazepma 20 mg was more marked than that by diazepam 5 mg. Comparison of these results with the data obtained from animal studies suggested that a myogenic factor might be more involved in P_1 latency and the level of consciousness in P_2 latency as previously described by us. From these results, the PPR test is considered to be a useful method for predicting clinical effects of anxiolytic drugs with several advantages; it may offer a physiological index for the effects of these drugs and it permits quantification of the responses and, accordingly, determination of equipotent doses of different drugs.
