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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.

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1. The 5‐hydroxytryptamine (5‐HT3) receptor antagonist, GR 38032F, which possesses potent anti‐emetic properties in vomiting induced by cancer chemotherapeutic drugs, has been tested to determine its value in the prophylaxis of motion sickness induced by cross‐coupled stimulation. The double‐blind trial compared GR 38032F with both a placebo (lactose) and with hyoscine. In addition, studies of ocular pursuit and saccadic eye movements were carried out following the administration of each drug. 2. The prophylactic effect of GR 38032F on motion‐induced nausea was indistinguishable from that of placebo, whereas following hyoscine subjects showed a highly significant (P less than 0.001) increase in tolerance to cross‐coupled stimulation. Tests of oculomotor function showed no effect on saccadic eye movement from either drug. However, both drugs produced a significant (P less than 0.05) though small reduction in eye velocity gain during pursuit eye movement. 3. These findings suggest that the 5‐HT3 receptor is not involved in the neural pathways that bring about motion sickness, but that it may have a role in the control of ocular pursuit. The absence of an anti‐motion sickness effect from a drug that is effective in the treatment of vomiting induced by cancer chemotherapy serves to emphasize that different neural mechanisms are involved in the generation of motion sickness.

On the ground, the essential requirement to remain orientated is a largely unconscious activity. In flight, orientation requires a conscious effort by the pilot particularly when the visual environment becomes degraded and a deceptive force environment becomes the frame of reference. Furthermore, an unusual force environment can determine the apparent location of objects within a limited visual scene, sometimes with disastrous consequences. This review outlines the sources of pilot disorientation that arise from the visual and force environment of flight and their interaction. It challenges the value of the traditional illusion-based approach to the subject both to aircrew and to surveys of disorientation. Also, it questions the emphasis on the shortcomings of vestibular function as the physiological basis for disorientation. While military accidents from all causes have shown a decline, there has been no corresponding reduction in accidents involving disorientation, 85% of which are the results of unrecognised disorientation. This finding has implications for the way in which pilots are taught about disorientation in the interest of enhanced flight safety. It argues for a greater use of conventional fixed base simulators to create disorientating scenarios rather than complex motion devices to create unusual sensations.