The Impact of Oral Promethazine on Human Whole-Body Motion Perceptual Thresholds

Abstract

Despite the widespread treatment of motion sickness symptoms using drugs and the involvement of the vestibular system in motion sickness, little is known about the effects of anti-motion sickness drugs on vestibular perception. In particular, the impact of oral promethazine, widely used for treating motion sickness, on vestibular perceptual thresholds has not previously been quantified. We examined whether promethazine (25 mg) alters vestibular perceptual thresholds in a counterbalanced, double-blind, within-subject study. Thresholds were determined using a direction recognition task (left vs. right) for whole-body yaw rotation, y-translation (interaural), and roll tilt passive, self-motions. Roll tilt thresholds were 31 % higher after ingestion of promethazine (P = 0.005). There were no statistically significant changes in yaw rotation and y-translation thresholds. This worsening of precision could have functional implications, e.g., during driving, bicycling, and piloting tasks. Differing results from some past studies of promethazine on the vestibulo-ocular reflex emphasize the need to study motion perception in addition to motor responses.

Keywords: anti-motion sickness drug; human experiments; medication; motion sickness; promethazine; vestibular perception.

Conflict of interest statement

Conflict of Interest

The authors declare that they have no conflict of interest.

Figures

FIG. 1

Six-degree-of-freedom MOOG platform device used to measure perceptual motion recognition thresholds. Three motion directions were tested: yaw rotation, y-translation, and roll tilt.

FIG. 2

During each one of the three testing motions (yaw rotation, y-translation, and roll tilt), participants were subjected to motion stimuli corresponding to single cycles of sinusoidal acceleration. An example of one cycle of sinusoidal acceleration of yaw rotation is shown in the bottom figure, and this corresponds to cosine bell velocity and sigmoidal displacement profiles. The example shown shows a 1-Hz motion (frequency used in yaw rotation and y-translation motions) with a displacement of 1 °.

FIG. 3

Example of subject responses fit with Gaussian cumulative distribution psychometric functions for roll tilt testing from one subject (top: placebo; bottom: promethazine). Circles represent the fraction rightward out of all responses at a given amplitude, where the size of the circle indicates the number of responses. In some cases, responses for stimuli within a 0.03 °/s interval were pooled for display only, but not for fitting analysis. The dashed line indicates the level where the subject perceived 84 % of the motions to be rightward, which is equal to the one-standard-deviation threshold after adjusting for the mean. These results show that, for this particular subject, promethazine increased the standard deviation and, therefore, the roll tilt threshold.

FIG. 4

Vestibular perceptual thresholds (a yaw rotation, b y-translation, and c roll tilt) measured for the same ten subjects in two conditions: with placebo and with promethazine. Gray lines represent individual subjects, and black lines represent the average, calculated as geometric mean, and standard deviation of the thresholds across subjects. Threshold data are presented using a logarithmic scale. There was a statistically significant change of +31 % in roll tilt thresholds (see c) after the intake of 25 mg of promethazine. Yaw rotation and y-translation thresholds showed an increase of +10 and +18 % with promethazine, although these changes were not statistically significant. d–f % Change in thresholds due to promethazine relative to placebo for each of the subjects (subjects are presented in the same order in each of the three panels).