Clinical pharmacology of a new antidepressant, Y-8894 in healthy young and elderly volunteers.

In the first experiment the influences of a single oral administration of a new antidepressant, Y-8894 50 mg, nortriptyline 50 mg, and placebo on physiological and psychological parameters were evaluated by a double-blind, crossover method in 10 healthy male volunteers. As the second experiment eight elderly healthy men were also recruited to examine the clinical pharmacology of Y-8894. Y-8894 50 mg showed no significant anticholinergic, sedative, or cardiovascular effect on any of the measures used in young subjects. In the elderly Y-8894 50 mg increased pulse rate (P less than 0.05-0.01), lowered systolic blood pressure (P less than 0.05-0.005), and decreased salivary flow (P less than 0.05) compared with those of pre-drug baseline. C.f.f. was improved after Y-8894 50 mg, but not significantly. Neither psychomotor performance nor immediate memory was influenced after either treatment in young subjects. Furthermore, in the elderly Y-8894 50 mg did not affect these parameters. In the elderly both k21 and ke were smaller, t1/2,z was longer, and AUC was larger compared with young subjects (P less than 0.01). In conclusion, Y-8894 50 mg seemed to lack the anticholinergic, sedative and cardiovascular effects which were observed after nortriptyline 50 mg in young subjects. In the elderly some affects were recognized, in part, due to pharmacokinetic alteration.