EFFECTS OF DIPHENHYDRAMINE ON HUMAN EYE-MOVEMENTS

Peak saccadic eye movement velocity (SEV) and average smooth pursuit g ain (SP) are reduced in a dose-dependent manner by diazepam and provid e reliable, quantitative measures of benzodiazepine agonist effects. T o evaluate the specificity of these eye movement effects for agents ac ting at the central GABA-benzodiazepine receptor complex and the role of sedation in benzodiazepine effects, we studied eye movement effects of diphenhydramine, a sedating drug which does not act at the GABA-be nzodiazepine receptor complex. Ten healthy males, aged 19-28 years, wi th no history of axis I psychiatric disorders or substance abuse, rece ived 50 mg/70 kg intravenous diphenhydramine or a similar volume of sa line on separate days 1 week apart. SEV, saccade latency and accuracy, SP, self-rated sedation, and short-term memory were assessed at basel ine and at 5, 15, 30, 45, 60, 90 and 120 min after drug administration . Compared with placebo, diphenhydramine produced significant SEV slow ing, and increases in saccade latency and self-rated sedation. There w as no significant effect of diphenhydramine on smooth pursuit gain, sa ccade accuracy, or short-term memory. These results suggest that, like diazepam, diphenhydramine causes sedation, SEV slowing, and an increa se in saccade latency. Since the degree of diphenhydramine-induced sed ation was not correlated with changes in SEV or saccade latency, slowi ng of saccadic eye movements is unlikely to be attributable to sedatio n alone. Unlike diazepam, diphenhydramine does not impair smooth pursu it gain, saccadic accuracy, or memory. Different neurotransmitter syst ems may influence the neural pathways involved in SEV and smooth pursu it gain.