Effects of the antihistaminergic drugs diphenhydramine and zolantidine on vestibular-induced hypothalamic neuronal activity in the guinea pig.

The mode of action of diphenhydramine in treating motion sickness is unknown. Using an electrophysiologic technique, we investigated the effects of intravenous diphenhydramine and zolantidine on the changes in neuronal activity produced by caloric stimulation in the hypothalamic paraventricular nucleus (PVN) in the guinea pig. Changes in neuronal activity were modulated by the administration of diphenhydramine in a high percentage of the neurons tested (71%), while zolantidine affected only a small number (29%). This finding reinforces the involvement of a histaminergic system in vestibular autonomic responses. The modulatory effect of diphenhydramine on PVN neuron activity may explain in part this drug's efficacy in treating motion sickness.