Control of nausea and autonomic dysfunction with terfenadine, a peripherally acting antihistamine

Abstract

Terfenadine (Seldane) was administered to 14 male subjects in a randomized, double-blinded, and crossed-over design to assess the efficacy of this peripherally active antihistamine as an anti-motion sickness drug. Terfenadine possesses practically no central side effects. A Staircase Profile Test was administered 4 h following placebo or a single oral dose of terfenadine (300 mg). The study revealed a statistically significant therapeutic effect from terfenadine (p less than 0.05). This led us to conclude that because the drug does not or only poorly crosses the blood-brain barrier, a selective peripheral antihistamine (H1) action may be sufficient in the control of motion sickness induced through cross-coupled accelerative semicircular canal stimulation using a rotating chair. This finding implies that other peripherally acting agents might be found that possess even greater anti-motion sickness efficacy. The present research raises additional questions regarding current theories on the etiology of motion sickness, its associated autonomic system dysfunction, and the validity of assumptions that effective pharmacological agents must act centrally.