Single and Repeated Dose Comparison of Three Antihistamines and Phenylpropanolamine: Psychomotor Performance and Subjective Appraisals of Sleep

1 In a double-blind cross-over study, nine healthy male students received placebo, brompheniramine 12 mg), carbinoxamine (12 mg), clemastine (1 mg), and phenylpropanolamine (50 mg) orally. Three doses of each drug were given: at 08.30 h and 21.00 h on the first day of treatment and at 08.30 h on the following day. 2 Psychomotor skills and subjective feelings were recorded before and 2, 6 and 12 h after the first dose on day 1 as well as before and 2 and 6 h after the third dose on day 2. Subjective appraisals of sleep were requested on the morning of day 2. 3 All antihistamines tended to cause subjective drowsiness on the first day of treatment. Drowsiness was felt for a maximum of 2 h after carbinoxamine, 6 h after brompheniramine, and 12 h after clemastine. In contrast to antihistamines, phenylpropanolamine made subjects more alert and quick witted. Tolerance to the antihistamine-induced drowsiness developed on the second day. 4 Divided attention, tracking, speed anticipation and sleep were not affected by any drug. Carbinoxamine slowed reactions 2 h after the first dose, but no impairment was measured in objective tests after brompheniramine or clemastine. 5 Phenylpropanolamine improved reaction speed and reaction accuracy and enhanced flicker recognition throughout the study. Phenylpropanolamine plasma levels and improvement in flicker fusion test results correlated with each other on day 2. 6 The results suggest that phenylpropanolamine and the antihistamines studied are comparatively harmless to psychomotor performance and driving skills.