The effects of the selective muscarinic M3 receptor antagonist darifenacin, and of hyoscine (scopolamine), on motion sickness, skin conductance & cognitive function

AimsThe aim of this study was to compare the effects of the selective M3 muscarinic acetylcholine receptor antagonist darifenacin, oral hyoscine hydrobromide and placebo on motion sickness induced by cross-coupled stimulation. MethodsThe effects of darifenacin 10mg or 20mg, hyoscine hydrobromide 0.6mg and placebo were assessed in a randomized, double-blind, four-way cross over trial of 16 healthy subjects. Motion sickness, skin conductance (a measure of sweating) and psychomotor cognitive function tests were investigated. ResultsHyoscine hydrobromide produced significantly increased tolerance to motion versus placebo (P<0.05 to P<0.01). The motion protection effect of darifenacin (10 or 20mg) was approximately one third that of hyoscine hydrobromide but was not significant versus placebo. Darifenacin and hyoscine hydrobromide both significantly reduced skin conductance versus placebo. Darifenacin produced either no effect or an enhanced effect on cognitive function in contrast to hyoscine hydrobromide, where there was significant impairment of psychomotor performance. ConclusionThe results suggest that selective antagonism of the M3 receptor may not be important in the prevention of motion sickness. However, selective M3 antagonism does not impair cognitive function. These observations may be important given that long-term treatment with non-selective anti-muscarinic agents such as oxybutynin may lead to an increased incidence of dementia.