Promethazine affects optokinetic but not vestibular responses in monkeys.
BACKGROUND
Promethazine is used to treat motion sickness including Space Adaptation Syndrome, but there is incomplete information about how it affects vestibular and optokinetic responses.


METHODS
Vestibular and optokinetic nystagmus, recorded with eye coils, were characterized in monkeys after administration of promethazine at dosages approximately equivalent to those used by humans in space.


RESULTS
The initial increase of horizontal eye velocity during optokinetic nystagmus (OKN) was reduced after receiving the drug. Consequently, it took a longer time for eye velocity to rise to 60% of steady state value, the normal initial jump in eye velocity. Steady state OKN, maximum gains of optokinetic after-nystagmus (OKAN) and OKAN falling time constants were unaffected. The gains and time constants of the horizontal, vertical and roll angular vestibulo-ocular reflex (aVOR), the amplitude and velocity of saccades, and ocular counter-rolling (OCR), induced by off-vertical axis rotation (OVAR) were unaffected by promethazine. A two-component optokinetic model simulated the data simply by reducing the gain of the initial (rapid) component of OKN. A reduction in coupling between a non-linear element and the velocity storage integrator was required to simulate some vertical OKN data.


CONCLUSIONS
Promethazine reduces the gain of the direct visual-oculomotor pathway in monkeys. It has little effect on saccades, the gain and time constant of the aVOR and the low frequency linear vestibulo-ocular reflex (IVOR), which orients the eyes during ocular counterrolling. The optokinetic deficit is consistent with reported reduction in ocular pursuit and VOR suppression after promethazine in humans.
Dai
M
M
Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, USA. mdai@smtplink.mssm.edu
Kaufmann
H
H
Raphan
T
T
Cohen
B
B
D000818:Animals; D006634:Histamine H1 Antagonists / Q000009:adverse effects*; D008252:Macaca fascicularis; D008954:Models, Biological; D017711:Nonlinear Dynamics; D017120:Nystagmus, Optokinetic / Q000187:drug effects*; D009760:Nystagmus, Physiologic / Q000187:drug effects; D011398:Promethazine / Q000009:adverse effects*; D012027:Reflex, Vestibulo-Ocular / Q000187:drug effects*; D012399:Rotation; D012438:Saccades / Q000187:drug effects; D013238:Stereotaxic Techniques
D006634:Histamine H1 Antagonists; D011398:Promethazine