Comparison of the effects of a selective muscarinic receptor antagonist and hyoscine (scopolamine) on motion sickness, skin conductance and heart rate

Abstract

Aims: Hyoscine (scopolamine), which is effective in the prophylaxis of motion sickness, shows similar binding affinities to all of the five known muscarinic receptor sub-types. The effectiveness of hyoscine was compared with zamifenacin (UK-76654), which binds selectively to the muscarinic M3 and m5 receptors. Methods: Eighteen subjects received hyoscine hydrobromide 0.6 mg, zamifenacin 20 mg, or placebo (double-blind cross-over design). Sessions were 1 week apart and the drug (oral) was given 90 min prior to a motion sickness test. Motion sickness was elicited by cross-coupled stimulation on a turntable. The rotational velocity was incremented by 2°s-1 every 30s, and a sequence (seq) of eight head movements of 45°was completed every 30s. Motion tolerance was assessed as the number of sequences of head movement required to achieve moderate nausea. Pulse rate was recorded before and at 1 and 2 h after drug administration. Skin conductance activity in the frequency band 0.005-0.48 Hz, an index of sweat gland activity, was measured using Ag/AgCl electrodes on the palmar surfaces of fingers and across the forehead. Results: Both zamifenacin and hyoscine produced an increase in tolerance to the motion challenge (P<0.01) with no significant difference between the two drugs (5.0 ± 1.6 vs 5.7 ± 1.6 seqs. respectively, mean ± s.e.mean). Compared with placebo or zamifenacin, pulse rate fell following hyoscine administration (9 beats min-1, P<0.01). Skin conductance was reduced following hyoscine compared with zamifenacin or placebo (P<0.001). Conclusions: These results suggest that compounds with selective M3 and/or m5 antagonism possess activity against motion sickness. Antagonism at these receptors may be the basis of the anti-motion sickness action of hyoscine.