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 M 3 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 M 3 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.

A Comparison of Intranasal and Oral Scopolamine for Motion Sickness Prevention in Military Personnel

“…8) with intranasal and oral scopolamine, similar to findings reported by Golding and Stott (1997) using oral scopolamine, Klocker et al, (2001) using intranasal scopolamine and Parrott (1989) administering transdermal scopolamine. The heart rate data from this study indicate that 0.4 mg of intranasal scopolamine and 0.8 mg of oral scopolamine significantly decreased heart rate more than placebo over time, with differences being found at 75, 90, 115, and 165 minutes post intranasal dose and 165 minutes post oral scopolamine dose.…”

“…A variety of pharmaceutical countermeasures have been tested for military and space environment application (i.e., anticholinergics, antihistamines, antimuscarinics, and CNS stimulants), with several decreasing the symptoms of motion sickness, but efficacy varies widely and detrimental performance side-effects are common (Cornum, Caldwell & Cornum, 1997;Cowings et al, 1996;Golding & Stott, 1997;Marcus & Furman, 2006;Putcha, 1999;Wood & Graybiel, 1968). The most widely used medication, and perhaps the most extensively researched, is the anticholinergic drug scopolamine.…”

Genome-wide Association Study Using Pooled DNA to Identify Candidate Markers Mediating Susceptibility to Postoperative Nausea and Vomiting

“…33 The connection of muscarinic acetylcholine receptor 3 subtype to PONV could be further reinforced by the nonspecific muscarinic receptor antagonists (e.g., scopolamine) being effective in the attenuation of motion sickness, a syndrome that seems to be closely related to PONV (i.e., previous history of either PONV or motion sickness are both major risk factors for PONV). 34,35 Previously published studies demonstrated that sequence variations in the promoter region of the CHRM3 gene may be associated with asthma, atopy, and early-onset type 2 diabetes. 36,37 The initial findings from the pooled assays were successfully replicated for only 4 of 24 SNPs in the validation cohort.…”

Electrodermal activity in patients with neurally mediated syncope

“…The phenomenon of increased EDA prior to syncope seems similar to sweating or EDA that commonly occurs with motion sickness [5,11,12]. As with NMS, EDA may precede symptoms of motion sickness.…”