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The new H1-receptor antagonist BW 825C and triprolidine (2.5 and 5 mg) were administered to 12 healthy male volunteers in a double blind placebo controlled, balanced, crossover design. Histamine antagonism was measured by assessment of flare and weal areas after intradermal injection of histamine. The 2 compounds were approximately equipotent in blocking the flare and weal response to intradermal histamine and had a similar duration of action. Triprolidine impaired performance of vigilance and reaction time (p less than 0.05) compared with placebo while BW 825C did not. Drowsiness measured using visual analogue scales followed both triprolidine treatments, but not BW 825C. BW 825C had a plasma half-life (t1/2) of 1.7 +/- 0.2 h and triprolidine of 4.6 +/- 4.3 h. The peak plasma level of BW 825C was approximately 6 times that of triprolidine. It was concluded that BW 825C might be a clinically active H1-antagonist with reduced sedative side-effects.

This study was conducted to examine the effects of acute doses of lamotrigine (LTG) and carbamazepine (CBZ) in healthy subjects and determine whether the low tendency to impairment with LTG observed in animals applied to humans. Twelve healthy men participated in a placebo-controlled, balanced, double-blind comparison of the drugs on a series of psychomotor, autonomic, sensory, and subjective variables. Variables were analyzed by analysis of variance, and p < 0.05 was considered significant. Adaptive tracking and body sway were impaired by CBZ 600 mg. CBZ 400 and 600 mg impaired smooth pursuit eye movements and also reduced mean peak saccadic velocity. No differences from placebo occurred after LTG. CBZ 600 mg increased heart rate (HR), but no drug-related changes were noted in pupil size, salivary secretion, visual near point, or subjective effects. During the controlled study, mean plasma CBZ concentrations at 2 and 6.5 h after the 600-mg dose were 5.28 and 5.36 micrograms/ml; after LTG 300 mg, they were 3.16 and 3.00 micrograms/ml. Increased CBZ saliva concentrations were significantly associated (p < 0.01) with impaired adaptive tracking, smooth and saccadic eye movements and increased HR, and plasma concentrations were associated with impaired eye movements and body sway.

1 Bupropion, a novel antidepressant, has been compared with nomifensine and dexamphetamine in a controlled double blind trial in 12 healthy volunteers. 2 Signals detected in an auditory vigilance test were increased by dexamphetamine 5 and 10 mg when compared with lactose dummy, but unaffected by bupropion 100 and 200 mg and nomifensine 100 mg. Auditory reaction time was decreased by dexamphetamine but unaffected by bupropion and nomifensine. 3 Heart rate was increased after all active treatments but the largest rise followed dexamphetamine 10 mg which differed from both lactose dummy and all other active treatments. Systolic blood pressure was higher after dexamphetamine 10 mg than all other treatments, none of which differed from lactose. No changes occurred in diastolic blood pressure. Pupil size increased after dexamphetamine 10 mg but no changes followed other treatments. 4 Visual analogue scales showed that subjects were more alert, attentive, proficient, excited, interested and elated after dexamphetamine but no changes followed bupropion or nomifensine. Subjects were able to recognise that they had received an active drug only after dexamphetamine 10 mg.5 Increased activity was seen in the 7.5-13.5 Hz and 13.5-26 Hz frequency bands of the electroencephalogram after dexamphetamine 10 mg but not after bupropion or nomifensine. 6 These findings in man suggest that neither of these two, non-sedative antidepressants possess amphetamine-like stimulant activity, and are discussed in relation to the animal pharmacology of the drugs.