EFFECTS OF DIPHENHYDRAMINE AND DIMENHYDRINATE ON VESTIBULAR NEURONAL ACTIVITY OF CAT: A SEARCH FOR THE LOCUS OF THEIR ANTIMOTION SICKNESS ACTION

¹ Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, New York

The effects of diphenhydramine and dimenhydrinate on vestibular neuronal activity were studied in 23 cats. The neuronal activity was enhanced by physical stimulation of the labyrinth via angular (turntable) or linear (swing) acceleration, or by electrical stimulation of one of the vestibular nerve branches with a bipolar electrode. Both diphenhydramine (1.5 mg/kg i. v.) and dimenthydrinate (2.5-5.0 mg/kg i. v.) suppressed the spontaneous as well as the enhanced vestibular neuronal firing. The depressant effect was observed one hour after drug administration and partial recovery was observed in some cases three to five hours thereafter. Electrical stimulation of the vestibular nerve branch with a single pulse evoked field potentials in the vestibular nuclei which were initially facilitated by diphenhydramine or dimenhydrinate (N₁ component only) and later depressed (both N₁ and N₂ components). The depressant effects were maximal at one hour after drug administration, and recovery occurred within four to six hours. These findings suggest that the antimotion sickness property of diphenhydramine and dimenhydrinate may be due to diminished excitability of the vestibular nuclear complex.