J F Golding1, J R Stott. 1. Division of Psychology, University of Westminster, London, UK.
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 degrees s-1 every 30 s, and a sequence (seq) of eight head movements of 45 degrees 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.
RCT Entities:
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 degrees s-1 every 30 s, and a sequence (seq) of eight head movements of 45 degrees 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.
Authors: Dhwanil A Dalwadi; Seongcheol Kim; Shahnawaz M Amdani; Zhenglan Chen; Ren-Qi Huang; John A Schetz Journal: Pharmacol Res Date: 2016-05-06 Impact factor: 7.658