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 30 s, and a sequence (seq) of eight head movements of 45° was completed every 30 s. 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.
Keywords: hyoscine, muscarinic receptors M3 m5 , motion sickness, coriolis, heart rate, skin conductance
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