Action of Dimenhydrinate (Dramamine) and Other Drugs on Vestibular Function

Safety, tolerability, pharmacokinetics and pharmacokinetic‐pharmacodynamic modelling of the novel H4 receptor inhibitor SENS‐111 using a modified caloric test in healthy subjects

“…The modest improvement (20–30%) in vertigo parameters obtained in healthy volunteers with our modified caloric test is consistent with that observed with standard of care treatments and with non‐clinical data in rats with severe vestibular dysfunction induced by kainate or arsanilate . A moderate effect on acute vertigo symptoms, such as in AUV, is usually recommended so as to avoid jeopardizing central compensation which is a critical component of effective recovery after acute peripheral loss.…”

“…The caloric test has rarely been used as a pharmacodynamic test either in healthy volunteers or in patients, and is thus not standardized. The effects of drugs used as standard of care in vertigo symptoms such as H 1 histamine receptors antagonists (meclizine, dimenhydrinate) or agonists (betahistine), H 3 receptor antagonists (betahistine) or anticholinergic agents (scopolamine) on parameters related to duration of induced vertigo symptoms (by modified calorics or more cumbersome tests such rotary chair, torsion or parallel swing) including nystagmus, are typically modest (less than 30% improvement) with large variability ; specifically, effects on nystagmus PSV are either mild or absent. In our study, the caloric test was done in healthy volunteers with colder water than usual (25°C instead of 30°C) in only one ear and induced only mild but still measurable nystagmus and vertigo.…”

Effect of the novel histamine H4 receptor antagonist SENS‐111 on spontaneous nystagmus in a rat model of acute unilateral vestibular loss

“…While few clinical studies of anti‐vertigo agents have directly measured their effects on nystagmus, the extent of improvement seen with SENS‐111 in the context of severe induced vertigo in our preclinical model is similar to that reported with historical and more recent agents, including standard of care treatments such as H 1 receptor antagonists (Gutner, Gould, & Batterman, ; Kiroglu et al, ; Mangabeira‐Albernaz, ; Martin & Oosterveld, ; Philipszoon, ).…”

The Effects of Potent Analgesics Upon Vestibular Function

“…Having thus established that meperidine, morphine and methadon stimulate the labyrinthine mechanism, it was felt from our previous studies on the pharmacology of dimenhydrinate that the use of this medication prior to the administration of these potent analgesics would offset their action upon the balance mechanism (10). This was borne out in two subjects in whom the vestibular effects of intramuscular meperidine were completely blocked by the use of 100 mgms.…”