title: Intranasal scopolamine affects the semicircular canals centrally and peripherally.
abstract: Space motion sickness (SMS), a condition caused by an intravestibular conflict, remains an important obstacle that astronauts encounter during the first days in space. Promethazine is currently the standard treatment of SMS, but scopolamine is used by some astronauts to prevent SMS. However, the oral and transdermal routes of administration of scopolamine are known to have substantial drawbacks. Intranasal administration of scopolamine ensures a fast absorption and rapid onset of therapeutic effect, which might prove to be suitable for use during spaceflights. The aim of this study was to evaluate the effects of intranasally administered scopolamine (0.4 mg) on the semicircular canals (SCCs) and the otoliths. This double-blind, placebo-controlled study was performed on 19 healthy male subjects. The function of the horizontal SCC and the vestibulo-ocular reflex, as well as the saccular function and utricular function, were evaluated. Scopolamine turned out to affect mainly the SCCs centrally and peripherally but also the utricles to a lesser extent. Centrally, the most probable site of action is the medial vestibular nucleus, where the highest density of muscarinic receptors has been demonstrated and afferent fibers from the SCCs and utricles synapse. Furthermore, our results suggest the presence of muscarinic receptors in the peripheral vestibular system on which scopolamine has a suppressive effect. Given the depressant actions on the SCCs, it is suggested that the pharmacodynamic effect of scopolamine may be attributed to the obliteration of intravestibular conflict that arises during (S)MS.
authors.affiliation: Antwerp University Research Centre for Equilibrium and Aerospace, Antwerp University Hospital and University of Antwerp, Antwerp, Belgium;
authors.forename: Aurélie P
authors.initials: AP
authors.lastname: Weerts
authors.affiliation: Biomedical Operations and Research Branch, NASA Johnson Space Center, Houston, Texas; and.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Putcha
authors.affiliation: School of Pharmacy, Department of Pharmaceutical Sciences, University of Maryland, Baltimore, Maryland.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Hoag
authors.affiliation: Antwerp University Research Centre for Equilibrium and Aerospace, Antwerp University Hospital and University of Antwerp, Antwerp, Belgium;
authors.forename: Emma
authors.initials: E
authors.lastname: Hallgren
authors.affiliation: Antwerp University Research Centre for Equilibrium and Aerospace, Antwerp University Hospital and University of Antwerp, Antwerp, Belgium;
authors.forename: Angelique
authors.initials: A
authors.lastname: Van Ombergen
authors.affiliation: Antwerp University Research Centre for Equilibrium and Aerospace, Antwerp University Hospital and University of Antwerp, Antwerp, Belgium; Biomedical Operations and Research Branch, NASA Johnson Space Center, Houston, Texas; and School of Pharmacy, Department of Pharmaceutical Sciences, University of Maryland, Baltimore, Maryland.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Van de Heyning
authors.affiliation: Antwerp University Research Centre for Equilibrium and Aerospace, Antwerp University Hospital and University of Antwerp, Antwerp, Belgium; floris.wuyts@uantwerpen.be.
authors.forename: Floris L
authors.initials: FL
authors.lastname: Wuyts
mesh_terms: D000280:Administration, Inhalation; D000281:Administration, Intranasal; D000328:Adult; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D018727:Muscarinic Antagonists / Q000008:administration & dosage; D059085:Nasal Sprays; D015990:Placebo Effect; D004856:Postural Balance / Q000187:drug effects / Q000502:physiology*; D012027:Reflex, Vestibulo-Ocular / Q000187:drug effects / Q000502:physiology*; D012444:Saccule and Utricle / Q000187:drug effects / Q000502:physiology*; D012601:Scopolamine / Q000008:administration & dosage*; D012665:Semicircular Canals / Q000187:drug effects / Q000502:physiology*; D016896:Treatment Outcome
chemical_list: D018727:Muscarinic Antagonists; D059085:Nasal Sprays; D012601:Scopolamine
keywords: acetylcholine antagonist; motion sickness; saccules; semicircular canals; space motion sickness; utricles