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Comparison of the central nervous system effects produced by six H1-receptor antagonists
F E Simons1, T G Fraser, J D Reggin
1Faculty of Medicine, University of Manitoba, Canada.
Background:
A comprehensive comparative study of the central nervous system (CNS) properties of newer H1-receptor antagonist is needed.
Objective:
Our objective was to investigate the central nervous system effects of a single manufacturer's recommended dose of six H1-receptor antagonists, using appropriate controls.
Methods:
Fifteen healthy subjects received astemizole 10 mg, cetirizine 10 mg, ketotifen 2 mg, loratadine 10 mg, terfenadine 60 mg, diphenhydramine 50 mg or placebo. Before and 2-2.5 h after dosing, cognitive function was assessed using the P300-event-related potential, somnolence was assessed using a subjective score, and histamine skin tests were performed.
Results:
In rank order from least to greatest effect on the P300 latency, the medications were: terfenadine, placebo, cetirizine, ketotifen, loratadine, astemizole and diphenhydramine. Only diphenhydramine increased the P300 latency significantly compared with baseline and placebo. Subjective somnolence was significantly greater than baseline and placebo after cetirizine, ketotifen and diphenhydramine. All the H1-receptor antagonists suppressed the histamine induced weal significantly compared with baseline.
Conclusions:
The H1-receptor antagonist tested affected cognitive functioning and somnolence to different extents, although all produced satisfactory peripheral H1-blockade.