, Volume 234, Issue 1, pp 63–71 | Cite as

Medications influencing central cholinergic neurotransmission affect saccadic and smooth pursuit eye movements in healthy young adults

  • Preshanta Naicker
  • Shailendra Anoopkumar-Dukie
  • Gary D. Grant
  • Justin J. KavanaghEmail author
Original Investigation



Acetylcholine is an important neuromodulator in the central nervous system, where it plays a significant role in central functions such as the regulation of movement.


This study investigated the pharmacological effects of over-the-counter anticholinergic medications on saccadic and smooth pursuit eye movements, in order to establish the significance of central cholinergic pathways in the control of these centrally regulated oculomotor processes.


Sixteen subjects (mean age 23 ± 3 years, 9 females) performed pro-saccadic, anti-saccadic and smooth pursuit eye movement tests, while an eye tracker collected eye movement data. Oculomotor assessments were performed pre-ingestion, 0.5 and 2 h post-ingestion of drugs with varying degrees of central anticholinergic properties. The drugs tested were promethazine, hyoscine hydrobromide, hyoscine butylbromide and placebo.


The drug intervention with stronger central anticholinergic properties, promethazine, decreased amplitude and increased velocity in the pro-saccadic task and increased duration in the anti-saccadic task. Promethazine, once again, was the only drug to decrease eye velocity in the smooth pursuit test.


The prominent effects of the stronger central anticholinergic promethazine, on saccadic and smooth pursuit eye movements, potentially conveys the significance of central cholinergic pathways in the control of these centrally regulated oculomotor processes.


Anticholinergic Saccadic eye movement Smooth pursuit Oculomotor Neurotransmitter 


  1. Aosaki T, Miura M, Suzuki T, Nishimura K, Masuda M (2010) Acetylcholine-dopamine balance hypothesis in the striatum: an update. Geriatr Gerontol Int 10:148–157. doi: 10.1111/j.1447-0594.2010.00588.x CrossRefGoogle Scholar
  2. Baumann-Birkbeck L, Grant GD, Anoopkumar-Dukie S, Kavanagh JJ (2014) Drowsiness and motor responses to consecutive daily doses of promethazine and loratadine. Clin Neurophysiol 125:2390–2396. doi: 10.1016/j.clinph.2014.03.026 CrossRefPubMedGoogle Scholar
  3. Benarroch EE (2012) Effects of acetylcholine in the striatum: recent insights and therapeutic implications. Neurology 79:274–281. doi: 10.1212/WNL.0b013e31825fe154 CrossRefPubMedGoogle Scholar
  4. Birdsall NJM, Hulme EC (1983) Muscarinic receptor subclasses. Trends Pharmacol Sci 4:459–463. doi: 10.1016/0165-6147(83)90493-5 CrossRefGoogle Scholar
  5. Corallo CE, Whitfield A, Wu A (2009) Anticholinergic syndrome following an unintentional overdose of scopolamine. Ther Clin Risk Manag 5:719–723. doi: 10.2147/tcrm.s6732 CrossRefPubMedPubMedCentralGoogle Scholar
  6. De Brouwer S, Yuksel D, Blohm G, Missal M, Lefèvre P (2002) What triggers catch-up saccades during visual tracking? J Neurophysiol 87:1646–1650. doi: 10.1152/jn.00432.2001 CrossRefPubMedGoogle Scholar
  7. Di Stasi LL, Catena A, Cañas JJ, Macknik SL, Martinez-Conde S (2013) Saccadic velocity as an arousal index in naturalistic tasks. Neurosci Biobehav Rev 37:968–975. doi: 10.1016/j.neubiorev.2013.03.011 CrossRefPubMedGoogle Scholar
  8. Ettinger U, Kumari V, Zachariah E, Galea A, Crawford TJ, Corr PJ, Taylor D, Das M, Sharma T (2003) Effects of procyclidine on eye movements in schizophrenia. Neuropsychopharmacol 28:2199–2208. doi: 10.1038/sj.npp.1300286 Google Scholar
  9. Galley N (1998) An enquiry into the relationship between activation and performance using saccadic eye movement parameters. Ergonomics 41:698–720. doi: 10.1080/001401398186865 CrossRefPubMedGoogle Scholar
  10. Glue P (1991) The pharmacology of saccadic eye movements. J Psychopharmacol 5:377–387. doi: 10.1177/026988119100500432 CrossRefPubMedGoogle Scholar
  11. Grace PM, Stanford T, Gentgall M, Rolan PE (2010) Utility of saccadic eye movement analysis as an objective biomarker to detect the sedative interaction between opioids and sleep deprivation in opioid-naive and opioid-tolerant populations. J Psychopharmacol 24:1–10. doi: 10.1177/0269881109352704 CrossRefGoogle Scholar
  12. Grossberg S, Srihasam K, Bullock D (2012) Neural dynamics of saccadic and smooth pursuit eye movement coordination during visual tracking of unpredictably moving targets. Neural Netw 27:1–20. doi: 10.1016/j.neunet.2011.10.011 CrossRefPubMedGoogle Scholar
  13. Hikosaka O, Takikawa Y, Kawagoe R (2000) Role of the basal ganglia in the control of purposive saccadic eye movements. Physiol Rev 80:953–978PubMedGoogle Scholar
  14. Hindmarch I, Shamsi Z, Stanley N, Fairweather DB (1999) A double-blind, placebo-controlled investigation of the effects of fexofenadine, loratadine and promethazine on cognitive and psychomotor function. Br J Clin Pharmacol 48:200–206. doi: 10.1046/j.1365-2125.1999.00993.x CrossRefPubMedPubMedCentralGoogle Scholar
  15. Hutton S, Crawford T, Gibbins H, Cuthbert I, Barnes T, Kennard C, Joyce E (2001) Short and long term effects of antipsychotic medication on smooth pursuit eye tracking in schizophrenia. Psychopharmacol 157:284–291. doi: 10.1007/s002130100803 CrossRefGoogle Scholar
  16. Hutton SB, Crawford TJ, Puri BK, Duncan LJ, Chapman M, Kennard C, Barnes TRE, Joyce EM (1998) Smooth pursuit and saccadic abnormalities in first-episode schizophrenia. Psychol Med 28:685–692. doi: 10.1017/S0033291798006722 CrossRefPubMedGoogle Scholar
  17. Jo SH, Hong HK, Chong SH, Lee HS, Choe H (2009) H1 antihistamine drug promethazine directly blocks hERG K+ channel. Pharmacol Res 60:429–437. doi: 10.1016/j.phrs.2009.05.008 CrossRefPubMedGoogle Scholar
  18. Kavanagh JJ, Grant GD, Anoopkumar-Dukie S (2012) Low dosage promethazine and loratadine negatively affect neuromotor function. Clin Neurophysiol 123:780–786. doi: 10.1016/j.clinph.2011.07.046 CrossRefPubMedGoogle Scholar
  19. Klawans HL, Rubovits R (1974) Effect of cholinergic and anticholinergic agents on tardive dyskinesia. J Neurol Neurosurg Psychiatry 37:941–947. doi: 10.1136/jnnp.37.8.941 CrossRefPubMedPubMedCentralGoogle Scholar
  20. Klinkenberg I, Blokland A (2010) The validity of scopolamine as a pharmacological model for cognitive impairment: a review of animal behavioral studies. Neurosci Biobehav Rev 34:1307–1350. doi: 10.1016/j.neubiorev.2010.04.001 CrossRefPubMedGoogle Scholar
  21. Kobayashi Y, Isa T (2002) Sensory-motor gating and cognitive control by the brainstem cholinergic system. Neural Netw 15:731–741. doi: 10.1016/S0893-6080(02)00059-X CrossRefPubMedGoogle Scholar
  22. Krueger D, Michel K, Allam S, Weiser T, Demir IE, Ceyhan GO, Zeller F, Schemann M (2013) Effect of hyoscine butylbromide (Buscopan ®) on cholinergic pathways in the human intestine. Neurogastroenterol Motil 25:530–539. doi: 10.1111/nmo.12156 CrossRefGoogle Scholar
  23. Liu H, Farley JM (2004) Effects of first and second generation antihistamines on muscarinic induced mucus gland cell ion transport. BMC Pharmacol 5:1–10. doi: 10.1186/1471-2210-5-8 Google Scholar
  24. Naicker P, Anoopkumar-Dukie S, Grant GD, Kavanagh JJ (2013) The effects of antihistamines with varying anticholinergic properties on voluntary and involuntary movement. Clin Neurophysiol 124:1840–1845. doi: 10.1016/j.clinph.2013.04.003 CrossRefPubMedGoogle Scholar
  25. Oliva GA, Bucci MP, Fioravanti R (1993) Impairment of saccadic eye movements by scopolamine treatment. Percept Mot Skills 76:159–167. doi: 10.2466/pms.1993.76.1.159 CrossRefPubMedGoogle Scholar
  26. Orban de Xivry JJ, Lefèvre P (2007) Saccades and pursuit: two outcomes of a single sensorimotor process. J Physiol 584:11–23. doi: 10.1113/jphysiol.2007.139881 CrossRefPubMedPubMedCentralGoogle Scholar
  27. Picciotto MR, Higley MJ, Mineur YS (2012) Acetylcholine as a neuromodulator: cholinergic signaling shapes nervous system function and behavior. Neuron 76:116–129. doi: 10.1016/j.neuron.2012.08.036 CrossRefPubMedPubMedCentralGoogle Scholar
  28. Reilly JL, Lencer R, Bishop JR, Keedy S, Sweeney JA (2008) Pharmacological treatment effects on eye movement control. Brain Cogn 68:415–435. doi: 10.1016/j.bandc.2008.08.026 CrossRefPubMedPubMedCentralGoogle Scholar
  29. Renner UD, Oertel R, Kirch W (2005) Pharmacokinetics and pharmacodynamics in clinical use of scopolamine. Ther Drug Monit 27:655–665CrossRefPubMedGoogle Scholar
  30. Snyder SH (1976) Action of anticholinergic drugs on striatal dopamine. Pharmacol Ther B 2:65–70. doi: 10.1016/0306-039X(76)90019-2 PubMedGoogle Scholar
  31. Squire L, Bloom FE, Spitzer NC, Squire LR, Berg D, du Lac S, Ghosh A (2008) Fundamental Neuroscience. Academic Press, CanadaGoogle Scholar
  32. Tytgat GN (2007) Hyoscine butylbromide: a review of its use in the treatment of abdominal cramping and pain. Drugs 67:1343–1357. doi: 10.2165/00003495-200767090-00007 CrossRefPubMedGoogle Scholar
  33. Walker R, Walker DG, Husain M, Kennard C (2000) Control of voluntary and reflexive saccades. Exp Brain Res 130:540–544. doi: 10.1007/s002219900285 CrossRefPubMedGoogle Scholar
  34. Wang J (2013) Anticholinergic side effects among the elderly. APHS Pharmacy Circuit:1–4Google Scholar
  35. Wilden J, Rapeport D (2004) Presumed central anticholinergic syndrome from inadvertent intravenous hyoscine hydrobromide (scopolamine) injection. Anaesth Intensive Care 32:419–422PubMedGoogle Scholar
  36. Yan Y-J, Cui D-M, Lynch JC (2001) Overlap of saccadic and pursuit eye movement systems in the brain stem reticular formation. J Neurophysiol 86:3056–3060PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Preshanta Naicker
    • 1
    • 2
  • Shailendra Anoopkumar-Dukie
    • 1
    • 2
  • Gary D. Grant
    • 1
    • 2
  • Justin J. Kavanagh
    • 1
    • 3
    Email author
  1. 1.Menzies Health InstituteGriffith UniversityGold CoastAustralia
  2. 2.School of PharmacyGriffith UniversityGold CoastAustralia
  3. 3.Centre for Musculoskeletal ResearchGriffith UniversityGold CoastAustralia

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