Skip to main content

Advertisement

Log in

The Impact of Oral Promethazine on Human Whole-Body Motion Perceptual Thresholds

  • Research Article
  • Published:
Journal of the Association for Research in Otolaryngology Aims and scope Submit manuscript

Abstract

Despite the widespread treatment of motion sickness symptoms using drugs and the involvement of the vestibular system in motion sickness, little is known about the effects of anti-motion sickness drugs on vestibular perception. In particular, the impact of oral promethazine, widely used for treating motion sickness, on vestibular perceptual thresholds has not previously been quantified. We examined whether promethazine (25 mg) alters vestibular perceptual thresholds in a counterbalanced, double-blind, within-subject study. Thresholds were determined using a direction recognition task (left vs. right) for whole-body yaw rotation, y-translation (interaural), and roll tilt passive, self-motions. Roll tilt thresholds were 31 % higher after ingestion of promethazine (P = 0.005). There were no statistically significant changes in yaw rotation and y-translation thresholds. This worsening of precision could have functional implications, e.g., during driving, bicycling, and piloting tasks. Differing results from some past studies of promethazine on the vestibulo-ocular reflex emphasize the need to study motion perception in addition to motor responses.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

FIG. 1
FIG. 2
FIG. 3
FIG. 4

Similar content being viewed by others

References

  • Bagian JP, Ward DF (1994) A retrospective study of promethazine and its failure to produce the expected incidence of sedation during space flight. J Clin Pharmacol 34(6):649–651

    Article  CAS  PubMed  Google Scholar 

  • Benson AJ et al (1986) Thresholds for the detection of the direction of whole-body, linear movement in the horizontal plane. Aviat Space Environ Med 57(11):1088–1096

    CAS  PubMed  Google Scholar 

  • Benson AJ et al (1989) Thresholds for the perception of whole body angular movement about a vertical axis. Aviat Space Environ Med 60(3):205–213

    CAS  PubMed  Google Scholar 

  • Bermúdez Rey MC, Clark TK, Wang W, Leeder T, Bian Y, Merfeld DM (2016). Vestibular perceptual thresholds increase above the age of 40. Front Neurol 7:162. doi:10.3389/fneur.2016.00162

  • Brainard A, Gresham C (2014) Prevention and treatment of motion sickness. Am Fam Physician 90(1):41–46

    PubMed  Google Scholar 

  • Brandt T et al (1974) Drug effectiveness on experimental optokinetic and vestibular motion sickness. Aerosp Med 45(11):1291–1297

    CAS  PubMed  Google Scholar 

  • Burke RE, Fahn S (1985) Choline acetyltransferase activity of the principal vestibular nuclei of rat, studied by micropunch technique. Brain Res 328(1):196–199

    Article  CAS  PubMed  Google Scholar 

  • Butler JS et al (2010) Bayesian integration of visual and vestibular signals for heading. J Vis 10(11):23

    Article  PubMed  Google Scholar 

  • Chaudhuri SE et al (2013) Whole-body motion-detection tasks can yield much lower thresholds than direction-recognition tasks: implications for the role of vibration. J Neurophysiol 110(12):2764–2772

    Article  PubMed  PubMed Central  Google Scholar 

  • Clarke PB et al (1985) Nicotinic binding in rat brain: autoradiographic comparison of [3H]acetylcholine, [3H]nicotine, and [125I]-alpha-bungarotoxin. J Neurosci 5(5):1307–1315

    CAS  PubMed  Google Scholar 

  • Colebatch JG et al (1994) Myogenic potentials generated by a click-evoked vestibulocollic reflex. J Neurol Neurosurg Psychiatry 57(2):190–197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Crane BT (2012) Fore-aft translation aftereffects. Exp Brain Res 219(4):477–487

    Article  PubMed  PubMed Central  Google Scholar 

  • Dai M et al (2003) The relation of motion sickness to the spatial-temporal properties of velocity storage. Exp Brain Res 151(2):173–189

    Article  PubMed  Google Scholar 

  • Davis JR et al (1993a) Comparison of treatment strategies for space motion sickness. Acta Astronaut 29(8):587–591

    Article  CAS  PubMed  Google Scholar 

  • Davis JR et al (1993b) Treatment efficacy of intramuscular promethazine for space motion sickness. Aviat Space Environ Med 64(3 Pt 1):230–233

    CAS  PubMed  Google Scholar 

  • Ernst MO, Banks MS (2002) Humans integrate visual and haptic information in a statistically optimal fashion. Nature 415(6870):429–433

    Article  CAS  PubMed  Google Scholar 

  • Fernie GR et al (1982) The relationship of postural sway in standing to the incidence of falls in geriatric subjects. Age Ageing 11(1):11–16

    Article  CAS  PubMed  Google Scholar 

  • Galvan-Garza R (2016) Enhancement of perception with the application of stochastic vestibular stimulation. Massachusetts Institute of Technology, Department of Aeronautics & Astronautics, Cambridge, MA

    Google Scholar 

  • Grabherr L et al (2008) Vestibular thresholds for yaw rotation about an earth-vertical axis as a function of frequency. Exp Brain Res 186(4):677–681

    Article  PubMed  Google Scholar 

  • Graybiel A et al (1965) Effects of exposure to a rotating environment (10 rpm) on four aviators for a period of twelve days. Aerosp Med 36:733–754

    CAS  PubMed  Google Scholar 

  • Green DM, Swets JA (1966) Signal detection theory and psychophysics. Wiley, New York

    Google Scholar 

  • Gu Y et al (2008) Neural correlates of multisensory cue integration in macaque MSTd. Nat Neurosci 11(10):1201–1210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guedry FE (1974) Psychophysics of vestibular sensation. In: Kornhuber HH (ed) Vestibular system part 2: psychophysics, applied aspects and general interpretations. Springer Berlin Heidelberg, Berlin, Heidelberg, pp 3–154

    Chapter  Google Scholar 

  • Haburcakova C et al (2012) Frequency dependence of vestibuloocular reflex thresholds. J Neurophysiol 107(3):973–983

    Article  PubMed  Google Scholar 

  • Hindmarch I et al (2002) An evaluation of the effects of high-dose fexofenadine on the central nervous system: a double-blind, placebo-controlled study in healthy volunteers. Clin Exp Allergy 32(1):133–139

    Article  CAS  PubMed  Google Scholar 

  • James W (1982) The sense of dizziness in deaf-mutes. Am J Otol 4:239–254

    Google Scholar 

  • Kaernbach C (2001) Slope bias of psychometric functions derived from adaptive data. Percept Psychophys 63(8):1389–1398

    Article  CAS  PubMed  Google Scholar 

  • Karmali, F. and D. M. Merfeld (2012). A distributed, dynamic, parallel computational model: the role of noise in velocity storage. J Neurophysiol 108(2):390–405

  • Karmali F et al (2014) Visual and vestibular perceptual thresholds each demonstrate better precision at specific frequencies and also exhibit optimal integration. J Neurophysiol 111(12):2393–2403

    Article  PubMed  Google Scholar 

  • Karmali F et al (2016a) Determining thresholds using adaptive procedures and psychometric fits: evaluating efficiency using theory, simulations, and human experiments. Exp Brain Res 234(3):773–789

    Article  PubMed  Google Scholar 

  • Karmali, F., et al. (2016b) Development of a countermeasure to enhance sensorimotor adaptation to altered gravity level. IEEE Aerospace Conference, Big Sky, MT

  • Lackner JR, Graybiel A (1994) Use of promethazine to hasten adaptation to provocative motion. J Clin Pharmacol 34(6):644–648

    Article  CAS  PubMed  Google Scholar 

  • Leek MR (2001) Adaptive procedures in psychophysical research. Percept Psychophys 63(8):1279–1292

    Article  CAS  PubMed  Google Scholar 

  • Leek MR et al (1992) Estimation of psychometric functions from adaptive tracking procedures. Percept Psychophys 51(3):247–256

    Article  CAS  PubMed  Google Scholar 

  • Lewis RF et al (2011) Abnormal motion perception in vestibular migraine. Laryngoscope 121(5):1124–1125

    Article  PubMed  PubMed Central  Google Scholar 

  • Lim K et al (2017) Perceptual precision of passive body tilt is consistent with statistically optimal cue integration. J Neurophysiol: jn 00073:02016

    Google Scholar 

  • Lin D et al (2008) Reliability of COP-based postural sway measures and age-related differences. Gait Posture 28(2):337–342

    Article  PubMed  Google Scholar 

  • Mah, R. W., et al. (1989). Threshold perception of whole-body motion to linear sinusoidal stimulation. AIAA Conference on Motion Cues in Flight Simulation and Simulator Induced Sickness, Boston, MA

  • McCullagh P, Nelder JA (1989) Generalized linear models. Chapman and Hall, London

    Book  Google Scholar 

  • Merfeld DM (2011) Signal detection theory and vestibular thresholds: I. Basic theory and practical considerations. Exp Brain Res 210(3–4):389–405

    Article  PubMed  PubMed Central  Google Scholar 

  • Merfeld DM et al (2005a) Vestibular perception and action employ qualitatively different mechanisms. I. Frequency response of VOR and perceptual responses during translation and tilt. J Neurophysiol 94(1):186–198

    Article  PubMed  Google Scholar 

  • Merfeld DM et al (2005b) Vestibular perception and action employ qualitatively different mechanisms. II. VOR and perceptual responses during combined Tilt&Translation. J Neurophysiol 94(1):199–205

    Article  PubMed  Google Scholar 

  • Merfeld DM et al (2016) Dynamics of individual perceptual decisions. J Neurophysiol 115(1):39–59

    Article  PubMed  Google Scholar 

  • Miller EF II, Graybiel A (1969) Effect of drugs on ocular counterrolling. Clin Pharmacol Ther 10(1):92–99

    Article  CAS  PubMed  Google Scholar 

  • Money KE, Cheung BS (1983) Another function of the inner ear: facilitation of the emetic response to poisons. Aviat Space Environ Med 54(3):208–211

    CAS  PubMed  Google Scholar 

  • Paton DM, Webster DR (1985) Clinical pharmacokinetics of H1 receptor antagonists (the antihistamines). Clin Pharmacokinet 10(6):477–497

    Article  CAS  PubMed  Google Scholar 

  • Roditi RE, Crane BT (2012) Suprathreshold asymmetries in human motion perception. Exp Brain Res 219(3):369–379

    Article  PubMed  PubMed Central  Google Scholar 

  • Rosenberg, M., et al. (2016) Sensory precision limits vehicle control performance. Human Research Program Investigator’s Workshop, Galveston, TX

  • Rotter A et al (1979) Muscarinic receptors in the central nervous system of the rat. II. Distribution of binding of [3H]propylbenzilylcholine mustard in the midbrain and hindbrain. Brain Res 180(2):167–183

    Article  CAS  PubMed  Google Scholar 

  • Schwartz RD (1986) Autoradiographic distribution of high affinity muscarinic and nicotinic cholinergic receptors labeled with [3H]acetylcholine in rat brain. Life Sci 38(23):2111–2119

    Article  CAS  PubMed  Google Scholar 

  • Soyka F et al (2011) Predicting direction detection thresholds for arbitrary translational acceleration profiles in the horizontal plane. Exp Brain Res 209(1):95–107

    Article  PubMed  PubMed Central  Google Scholar 

  • Strenkoski-Nix LC et al (2000) Pharmacokinetics of promethazine hydrochloride after administration of rectal suppositories and oral syrup to healthy subjects. Am J Health Syst Pharm 57(16):1499–1505

    CAS  PubMed  Google Scholar 

  • Taylor MM, Creelman CD (1967) PEST: efficient estimates on probability functions. The Journal of the Acoustical Society of America 41(4A):782–787

    Article  Google Scholar 

  • Treutwein B (1995) Adaptive psychophysical procedures. Vis Res 35(17):2503–2522

    Article  CAS  PubMed  Google Scholar 

  • Treutwein B, Strasburger H (1999) Fitting the psychometric function. Percept Psychophys 61(1):87–106

    Article  CAS  PubMed  Google Scholar 

  • Valko Y et al (2012) Vestibular labyrinth contributions to human whole-body motion discrimination. J Neurosci 32(39):13537–13542

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vanspauwen R et al (2011) No effects of anti-motion sickness drugs on vestibular evoked myogenic potentials outcome parameters. Otol Neurotol 32(3):497–503

    Article  PubMed  Google Scholar 

  • Wamsley JK et al (1981) Autoradiographic localization of muscarinic cholinergic receptors in rat brainstem. J Neurosci 1(2):176–191

    CAS  PubMed  Google Scholar 

  • Weerts AP et al (2012) Pharmaceutical countermeasures have opposite effects on the utricles and semicircular canals in man. Audiol Neurootol 17(4):235–242

    Article  CAS  PubMed  Google Scholar 

  • Weerts AP et al (2013) Baclofen affects the semicircular canals but not the otoliths in humans. Acta Otolaryngol 133(8):846–852

    Article  PubMed  Google Scholar 

  • Weerts AP et al (2014) Evaluation of the effects of anti-motion sickness drugs on subjective sleepiness and cognitive performance of healthy males. J Psychopharmacol 28(7):655–664

    Article  CAS  PubMed  Google Scholar 

  • Weerts AP et al (2015) Restricted sedation and absence of cognitive impairments after administration of intranasal scopolamine. J Psychopharmacol 29(12):1231–1235

    Article  CAS  PubMed  Google Scholar 

  • Wood CD, Graybiel A (1972) Theory of anti-motion sickness drug mechanisms. Aerospace Medicine 43(3):249–252

    CAS  PubMed  Google Scholar 

  • Wood CD et al (1985) Evaluation of antimotion sickness drug side effects on performance. Aviat Space Environ Med 56(4):310–316

    CAS  PubMed  Google Scholar 

  • Wyeth (2004). Oral Phenergan (promethazine HCl) prescribing information. http://www.accessdata.fda.gov/drugsatfda_docs/label/2004/07935s030lbl.pdf.

  • Yates BJ et al (2014) Integration of vestibular and emetic gastrointestinal signals that produce nausea and vomiting: potential contributions to motion sickness. Exp Brain Res 232(8):2455–2469

    Article  PubMed  PubMed Central  Google Scholar 

  • Zanni M et al (1995) Distribution of neurotransmitters, neuropeptides, and receptors in the vestibular nuclei complex of the rat: an immunocytochemical, in situ hybridization and quantitative receptor autoradiographic study. Brain Res Bull 36(5):443–452

    Article  CAS  PubMed  Google Scholar 

  • Zupan LH, Merfeld DM (2008) Interaural self-motion linear velocity thresholds are shifted by roll vection. Exp Brain Res 191(4):505–511

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We appreciate the participation of our anonymous subjects. We thank the Jenks Vestibular Physiology Lab for the use of the MOOG device and Dr. Dan Merfeld for his scientific insight and assistance using his MOOG device. We appreciate the assistance of Christine Finn at the Massachusetts Eye and Ear Infirmary pharmacy. This research was supported by the National Space Biomedical Research Institute through NASA NCC 9-58 and by the National Institutes of Health through NIDCD DC013635 (FK). Preliminary results have been presented at a conference (Karmali et al. 2016b).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ana Diaz-Artiles.

Ethics declarations

Informed consent was obtained from all subjects prior to participation. The study was approved by the Institutional Review Board (IRB) at the Massachusetts Eye and Ear Infirmary (MEEI) and the Committee on the Use of Humans as Experimental Subjects (COUHES) at Massachusetts Institute of Technology (MIT) in accordance with the ethical standards laid down in the 1975 Declaration of Helsinki, as revised in 2000.

Conflict of Interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Diaz-Artiles, A., Priesol, A.J., Clark, T.K. et al. The Impact of Oral Promethazine on Human Whole-Body Motion Perceptual Thresholds. JARO 18, 581–590 (2017). https://doi.org/10.1007/s10162-017-0622-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10162-017-0622-z

Keywords

Navigation