(--)-Hyoscine and cyclizine as motion sickness remedies.

There is much well-documented evidence for the efficacy of ()-hyoscine in the prevention of motion sickness in man, and this has been drawn from experiments carried out in a variety of situations (Brand & Perry, 1966). However, in most of these studies the drug was given at single fixed dose levels, usually 1 mg of the hydrobromide (0.7 mg (-)-hyoscine base), with the result that the dose-response relationship of the drug has never been clearly defined. The relative activity of different dose levels of the drug is thus unknown, as is its potency relative to that of other motion sickness drugs. Although 1 mg of the hydrobromide protected some 95% of subjects in the various trials, it also gave rise to troublesome complaints of dry mouth and blurred vision (Chinn, Bayne-Jones, Gersoni, Henderson, Zeransky, Schein, Karsner, Phillips, Yarbrough, Duffner, Kinsey, Melton, Voas, Jones, Maag, Trumbull, Shaw, Smith, Bauer, Sweeney & Weiner, 1956; Brand, McCance & Perry, 1963). It is also known to cause drowsiness and impair mental performance (Colquhoun, 1962). However, recent work has shown that the anti-emetic potency of (-)-hyoscine does not depend on peripheral antiacetylcholine activity, and there are indications that the drug may give good protection against motion sickness at doses much smaller than those used previously (Brand & Perry, 1966). This raises the possibility that a good anti-emetic effect might be obtained with doses less than 0.7 mg of the base, together with a reduction of unpleasant peripheral effects. There is also, as yet, no dose/response information for the depressant central effects of the drug (which might, for example, produce an impairment in mental efficiency), so it is not possible to state whether this depressant effect would be present at doses low enough not to produce troublesome dry mouth or blurred vision. There is, however, some evidence that the effect of the drug on certain mental performance tests at a dose of 0.7 mg of the base is small (Colquhoun, 1962). A similar situation exists with regard to cyclizine hydrochloride. The results of several trials show that it is undoubtedly effective in preventing motion-sickness (Brand & Perry, 1966), but since most of the studies were made at single dose levels (50 mg), no