Pharmaceutical countermeasures have opposite effects on the utricles and semicircular canals in man.

INTRODUCTION: Sensory conflicts in the vestibular system lead to motion sickness of which space motion sickness (SMS) is a special case. SMS affects up to 70% of the astronauts during the first 3 days in space. The search for effective countermeasures has led to several nonpharmacological and pharmacological approaches. The current study focuses on the effects of lorazepam (1 mg), meclizine (25 mg), promethazine (25 mg), and scopolamine (0.4 mg) on the vestibular system, with special focus on the canal and otolith functions separately. METHODS: The study had a placebo-controlled, single blind, repeated measures design. Sixteen healthy volunteers were subjected to a total of 7 test sessions, the first and last being without intake of medication. Semicircular canal function was evaluated by means of electronystagmography and otolith function with unilateral centrifugation. The horizontal semicircular canal function was characterized by the vestibulo-ocular reflex (VOR) gain measured during earth vertical axis rotation as well as the total caloric response. The function of the utricles was represented by the utricular sensitivity, reflecting the ocular counter roll relative to the virtual induced head tilt. RESULTS: Promethazine significantly decreased the semicircular canal and utricular parameters. Both scopolamine and lorazepam caused only a decrease in the utricular sensitivity, whereas meclizine only decreased the semicircular canal-induced VOR gain. DISCUSSION: The results show that the drugs affected different areas of the vestibular system and that the effects can thus be attributed to the specific pharmacological properties of each drug. Meclizine, as an antihistaminergic and weak anticholinergic drug, only affected the VOR gain, suggesting a central action on the medial vestibular nucleus. The same site of action is suggested for the anticholinergic scopolamine since acetylcholine receptors are present and utricular fibers terminate here. The global vestibular suppression caused by promethazine is probably a consequence of its anticholinergic, antihistaminergic, and antidopaminergic properties. Based on the fact that lorazepam increased the affinity of gamma-aminobutyric acid (GABA) for the GABA(A)-receptor and its effects on the utriculi, the site of action seems to be the lateral vestibular nucleus. CONCLUSION: Meclizine, scopolamine, and lorazepam selectively suppress specific parts of the vestibular system. Selective suppression of different parts of the vestibular system may be more beneficial for alleviating (space) motion sickness than general suppressive agents. Additionally, this knowledge may help the clinician in his therapeutic management of patients with either semicircular canal or otolith dysfunction.

Utricular sensitivity and preponderance assessed by the unilateral centrifugation test.

Utricular sensitivity and preponderance of the right or left utricle can be assessed by means of the unilateral centrifugation test. In this test, subjects are rotated about an earth vertical axis at a velocity of 400 degrees per second. During the ongoing rotation, the subject is gradually translated 4 cm first to the right, and then to the left, along an interaural axis, to a position at which one utricle becomes aligned with the axis of rotation, and at this point is subjected only to gravitational forces. At this eccentric position, the contralateral utricle is exposed to the combination of gravity and a centrifugal acceleration of 0.4g, corresponding to an apparent roll-tilt of 21.7 degrees. This stimulus induces ocular counterrolling (OCR), which is measured on-line using three-dimensional video-oculography (VOG). We observed that ocular counterrolling appears as a linear function of the gravito-inertial acceleration tilt of the head centre (GIA(HC)) during the lateral translation. We present a theoretical model for this linear relationship that contains two parameters: 1) the slope of the linear regression is a measure for the utricular sensitivity and 2) the intercept of the linear regression is a measure of the preponderance of the right or left utricle. The strength of the model is supported by data obtained from 28 healthy subjects and 14 patients with unilateral vestibular deafferentiation (UVD) due to acoustic neuroma surgery.