COMPARISON OF THE EFFECTS OF A SELECTIVE MUSCARINIC RECEPTOR ANTAGONIST AND HYOSCINE (SCOPOLAMINE) ON MOTION SICKNESS, SKIN-CONDUCTANCE ANDHEART-RATE

Aims Hyoscine (scopolamine), which is effective in the prophylaxis of motion sickness, shows similar binding affinities to all of the five k nown muscarinic receptor sub-types. The effectiveness of hyoscine was compared with zamifenacin (UK-76654), which binds selectively to the m uscarinic Mg and m5 receptors. Methods Eighteen subjects received hyos cine 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 upled s timulation on a turntable. The rotational velocity was incremented by 2 degrees s every 30 s, and a sequence (seq) of eight head movements o f 45 degrees was completed every 30 s. Motion tolerance was assessed a s the number of sequences of head movement required to achieve moderat e nausea. Pulse rate was recorded before and at 1 and 2 h after drug a dministration. Skin conductance activity in the frequency band 0.005-0 .48 Hz, an index of sweat gland activity, was measured using Ag/AgCl e lectrodes on the palmar surfaces of fingers and across the forehead. R esults Both zamifenacin and hyoscine produced an increase in tolerance to the motion challenge (P < 0.01) with no significant difference bet ween the two drugs (5.0 +/- 1.6 vs 5.7 +/- 1.6 seqs. respectively, mea n +/- s.e.mean). Compared with placebo or zamifenacin, pulse rate fell following hyoscine administration (9 beats min P < 0.01). Skin conduc tance was reduced following hyoscine compared with zamifenacin or plac ebo (P < 0.001). Conclusions These results suggest that compounds with selective Mg and/or m5 antagonism possess activity against motion sic kness. Antagonism at these receptors may be the basis of the anti-moti on sickness action of hyoscine.