title: Pharmaceutical countermeasures have opposite effects on the utricles and semicircular canals in man.
abstract: BACKGROUND
  Sensory conflicts in the vestibular system lead to motion sickness of which space motion sickness (SMS) is a special case. SMS affects up to 70% of the astronauts during the first 3 days in space. The search for effective countermeasures has led to several nonpharmacological and pharmacological approaches. The current study focuses on the effects of lorazepam (1 mg), meclizine (25 mg), promethazine (25 mg), and scopolamine (0.4 mg) on the vestibular system, with special focus on the canal and otolith functions separately.
  
  
  METHODS
  The study had a placebo-controlled, single blind, repeated measures design. Sixteen healthy volunteers were subjected to a total of 7 test sessions, the first and last being without intake of medication. Semicircular canal function was evaluated by means of electronystagmography and otolith function with unilateral centrifugation. The horizontal semicircular canal function was characterized by the vestibulo-ocular reflex (VOR) gain measured during earth vertical axis rotation as well as the total caloric response. The function of the utricles was represented by the utricular sensitivity, reflecting the ocular counter roll relative to the virtual induced head tilt.
  
  
  RESULTS
  Promethazine significantly decreased the semicircular canal and utricular parameters. Both scopolamine and lorazepam caused only a decrease in the utricular sensitivity, whereas meclizine only decreased the semicircular canal-induced VOR gain.
  
  
  CONCLUSIONS
  The results show that the drugs affected different areas of the vestibular system and that the effects can thus be attributed to the specific pharmacological properties of each drug. Meclizine, as an antihistaminergic and weak anticholinergic drug, only affected the VOR gain, suggesting a central action on the medial vestibular nucleus. The same site of action is suggested for the anticholinergic scopolamine since acetylcholine receptors are present and utricular fibers terminate here. The global vestibular suppression caused by promethazine is probably a consequence of its anticholinergic, antihistaminergic, and antidopaminergic properties. Based on the fact that lorazepam increased the affinity of gamma-aminobutyric acid (GABA) for the GABA(A)-receptor and its effects on the utriculi, the site of action seems to be the lateral vestibular nucleus.
  
  
  CONCLUSIONS
  Meclizine, scopolamine, and lorazepam selectively suppress specific parts of the vestibular system. Selective suppression of different parts of the vestibular system may be more beneficial for alleviating (space) motion sickness than general suppressive agents. Additionally, this knowledge may help the clinician in his therapeutic management of patients with either semicircular canal or otolith dysfunction.
authors.affiliation: Antwerp University Research Centre for Equilibrium and Aerospace (AUREA), Edegem, Belgium.
authors.forename: Aurélie P
authors.initials: AP
authors.lastname: Weerts
authors.forename: Guido
authors.initials: G
authors.lastname: De Meyer
authors.forename: Griet
authors.initials: G
authors.lastname: Pauwels
authors.forename: Robby
authors.initials: R
authors.lastname: Vanspauwen
authors.forename: John L
authors.initials: JL
authors.lastname: Dornhoffer
authors.forename: Paul H
authors.initials: PH
authors.lastname: Van de Heyning
authors.forename: Floris L
authors.initials: FL
authors.lastname: Wuyts
mesh_terms: D000328:Adult; D000932:Antiemetics / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008140:Lorazepam / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008468:Meclizine / Q000494:pharmacology / Q000627:therapeutic use; D008875:Middle Aged; D011398:Promethazine / Q000494:pharmacology / Q000627:therapeutic use; D012027:Reflex, Vestibulo-Ocular / Q000187:drug effects* / Q000502:physiology; D012444:Saccule and Utricle / Q000187:drug effects* / Q000503:physiopathology; D012601:Scopolamine / Q000494:pharmacology / Q000627:therapeutic use; D012665:Semicircular Canals / Q000187:drug effects* / Q000503:physiopathology; D018489:Space Motion Sickness / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control*; D014724:Vestibular Function Tests
chemical_list: D000932:Antiemetics; D008468:Meclizine; D012601:Scopolamine; D011398:Promethazine; D008140:Lorazepam