Injections of calmidazolium chloride into the ipsilateral medial vestibular nucleus or fourth ventricle reduce spontaneous ocular nystagmus following unilateral labyrinthectomy in guinea pigs.

Abstract

The effects of three injections (0.5-4.5 h post-operation) of 1-[bis-(p-chlorophenyl)methyl]-3-[2,4-dichloro-beta-(2,4- dichlorobenzyloxy)phenethyl]-imidazolium chloride (calmidazolium chloride, R24571), into the ipsilateral medial vestibular nucleus or fourth ventricle, on vestibular compensation for unilateral labyrinthectomy was studied in guinea pigs. R24571, a calmodulin antagonist and inhibitor of several Ca(2+)-dependent enzymes, caused a significant reduction in the average frequency of spontaneous ocular nystagmus (spontaneous nystagmus) during the first 53 h following unilateral labyrinthectomy (n = 5), compared with vehicle-injected animals (n = 5). Although a statistical analysis was not performed on the yaw head tilt and roll head tilt data because of the large variability between animals over the 53-h period of compensation, most R24571-treated animals had less yaw head tilt (4/4 animals) and roll head tilt (4/5 animals) at 9-11 h post-labyrinthectomy than the average values for the vehicle groups at that time. The decrease in the frequency of spontaneous nystagmus following R24571 treatment was not associated with general ataxia or sedation. These results are consistent with recent biochemical studies in suggesting that intracellular pathways associated with Ca2+ may be involved in the neuronal mechanisms of vestibular compensation following unilateral labyrinthectomy.