AbstractThe effects of three dose regimens of HOE 8476, a combination of nomifensine (25 mg) and clobazam (7.5 mg), placebo, and a combination of amitriptyline (25 mg) and chlordiazepoxide (10 mg) were compared in a five‐period double‐blind randomised crossover study. Ten healthy volunteer drivers took part in the study, and were tested at weekly intervals preceded by a 48‐hr predosing period and followed by a 4‐day washout period. The sedative activity of amitriptyline/chlordiazepoxide (AMI/CHLOR) was shown on nearly all the subjective and objective measures of behavior employed, while, in contrast, there was a relative lack of sedation and performance impairment attributed to HOE 8476, except with complex tasks at the higher dose level. The results of the study confirm previous results in volunteers that HOE 8476 has psychotropic activity which differs from that of a standard antidepressant/benzodiazepine combination in that it is not accompanied by significant sedation or impairment of psychomotor perf