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British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1989 Feb;27(2):147–157. doi: 10.1111/j.1365-2125.1989.tb05345.x

The effect on motion sickness and oculomotor function of GR 38032F, a 5-HT3-receptor antagonist with anti-emetic properties.

J R Stott 1, G R Barnes 1, R J Wright 1, C J Ruddock 1
PMCID: PMC1379774  PMID: 2523720

Abstract

1. The 5-hydroxytryptamine (5-HT3) receptor antagonist, GR 38032F, which possesses potent anti-emetic properties in vomiting induced by cancer chemotherapeutic drugs, has been tested to determine its value in the prophylaxis of motion sickness induced by cross-coupled stimulation. The double-blind trial compared GR 38032F with both a placebo (lactose) and with hyoscine. In addition, studies of ocular pursuit and saccadic eye movements were carried out following the administration of each drug. 2. The prophylactic effect of GR 38032F on motion-induced nausea was indistinguishable from that of placebo, whereas following hyoscine subjects showed a highly significant (P less than 0.001) increase in tolerance to cross-coupled stimulation. Tests of oculomotor function showed no effect on saccadic eye movement from either drug. However, both drugs produced a significant (P less than 0.05) though small reduction in eye velocity gain during pursuit eye movement. 3. These findings suggest that the 5-HT3 receptor is not involved in the neural pathways that bring about motion sickness, but that it may have a role in the control of ocular pursuit. The absence of an anti-motion sickness effect from a drug that is effective in the treatment of vomiting induced by cancer chemotherapy serves to emphasize that different neural mechanisms are involved in the generation of motion sickness.

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Selected References

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  1. Baloh R. W., Sharma S., Moskowitz H., Griffith R. Effect of alcohol and marijuana on eye movements. Aviat Space Environ Med. 1979 Jan;50(1):18–23. [PubMed] [Google Scholar]
  2. Barnes G. R. A procedure for the analysis of nystagmus and other eye movements. Aviat Space Environ Med. 1982 Jul;53(7):676–682. [PubMed] [Google Scholar]
  3. Barnes G. R., Crombie J. W., Edge A. The effects of ethanol on visual-vestibular interaction during active and passive head movements. Aviat Space Environ Med. 1985 Jul;56(7):695–701. [PubMed] [Google Scholar]
  4. Barnes G. R., Donnelly S. F., Eason R. D. Predictive velocity estimation in the pursuit reflex response to pseudo-random and step displacement stimuli in man. J Physiol. 1987 Aug;389:111–136. doi: 10.1113/jphysiol.1987.sp016649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bittencourt P. R., Wade P., Smith A. T., Richens A. The relationship between peak velocity of saccadic eye movements and serum benzodiazepine concentration. Br J Clin Pharmacol. 1981 Oct;12(4):523–533. doi: 10.1111/j.1365-2125.1981.tb01261.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Colby E. D., McCarthy L. E., Borison H. L. Emetic action of xylazine on the chemoreceptor trigger zone for vomiting in cats. J Vet Pharmacol Ther. 1981 Jun;4(2):93–96. doi: 10.1111/j.1365-2885.1981.tb00716.x. [DOI] [PubMed] [Google Scholar]
  7. Costall B., Domeney A. M., Naylor R. J., Tattersall F. D. 5-Hydroxytryptamine M-receptor antagonism to prevent cisplatin-induced emesis. Neuropharmacology. 1986 Aug;25(8):959–961. doi: 10.1016/0028-3908(86)90030-4. [DOI] [PubMed] [Google Scholar]
  8. Cunningham D., Hawthorn J., Pople A., Gazet J. C., Ford H. T., Challoner T., Coombes R. C. Prevention of emesis in patients receiving cytotoxic drugs by GR38032F, a selective 5-HT3 receptor antagonist. Lancet. 1987 Jun 27;1(8548):1461–1463. doi: 10.1016/s0140-6736(87)92208-2. [DOI] [PubMed] [Google Scholar]
  9. Davis B. M., Davis K. L. CKholinergic mechanisms and anterior pituitary hormone secretion. Biol Psychiatry. 1980 Apr;15(2):303–310. [PubMed] [Google Scholar]
  10. Eckmiller R. Neural control of pursuit eye movements. Physiol Rev. 1987 Jul;67(3):797–857. doi: 10.1152/physrev.1987.67.3.797. [DOI] [PubMed] [Google Scholar]
  11. Henn V., Cohen B. Coding of information about rapid eye movements in the pontine reticular formation of alert monkeys. Brain Res. 1976 May 28;108(2):307–325. doi: 10.1016/0006-8993(76)90188-8. [DOI] [PubMed] [Google Scholar]
  12. Jäntti V., Lang A. H., Keskinen E., Lehtinen I., Pakkanen A. Acute effects of intravenously given alcohol on saccadic eye movements and subjective evaluations of intoxication. Psychopharmacology (Berl) 1983;79(2-3):251–255. doi: 10.1007/BF00427822. [DOI] [PubMed] [Google Scholar]
  13. Jürgens R., Becker W., Kornhuber H. H. Natural and drug-induced variations of velocity and duration of human saccadic eye movements: evidence for a control of the neural pulse generator by local feedback. Biol Cybern. 1981;39(2):87–96. doi: 10.1007/BF00336734. [DOI] [PubMed] [Google Scholar]
  14. Kirsten E. B., Sharma J. N. Characteristicas and response differences to iontophoretically applied norepinephrine, D-amphetamine and acetylcholine on neurons in the medial and lateral vestibular nuclei of the cat. Brain Res. 1976 Aug 6;112(1):77–90. doi: 10.1016/0006-8993(76)90335-8. [DOI] [PubMed] [Google Scholar]
  15. Kohl R. L. Failure of metoclopramide to control emesis or nausea due to stressful angular or linear acceleration. Aviat Space Environ Med. 1987 Feb;58(2):125–131. [PubMed] [Google Scholar]
  16. Lehtinen I., Lang A. H., Jäntti V., Keskinen E. Acute effects of alcohol on saccadic eye movements. Psychopharmacology (Berl) 1979 May 8;63(1):17–23. doi: 10.1007/BF00426915. [DOI] [PubMed] [Google Scholar]
  17. Lehtinen I., Nyrke T., Lang A. H., Pakkanen A., Keskinen E. Quantitative effects of ethanol infusion on smooth pursuit eye movements in man. Psychopharmacology (Berl) 1982;77(1):74–80. doi: 10.1007/BF00436102. [DOI] [PubMed] [Google Scholar]
  18. Leibundgut U., Lancranjan I. First results with ICS 205-930 (5-HT3 receptor antagonist) in prevention of chemotherapy-induced emesis. Lancet. 1987 May 23;1(8543):1198–1198. doi: 10.1016/s0140-6736(87)92159-3. [DOI] [PubMed] [Google Scholar]
  19. Lucot J. B., Crampton G. H. Buspirone blocks motion sickness and xylazine-induced emesis in the cat. Aviat Space Environ Med. 1987 Oct;58(10):989–991. [PubMed] [Google Scholar]
  20. Miller E. F., 2nd, Graybiel A. A provocative test for grading susceptibility to motion sickness yielding a single numerical score. Acta Otolaryngol Suppl. 1970;274:1–20. [PubMed] [Google Scholar]
  21. Optican L. M., Robinson D. A. Cerebellar-dependent adaptive control of primate saccadic system. J Neurophysiol. 1980 Dec;44(6):1058–1076. doi: 10.1152/jn.1980.44.6.1058. [DOI] [PubMed] [Google Scholar]
  22. ROBINSON D. A. THE MECHANICS OF HUMAN SACCADIC EYE MOVEMENT. J Physiol. 1964 Nov;174:245–264. doi: 10.1113/jphysiol.1964.sp007485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Reason J. T. Relations between motion sickness susceptibility, the spiral after-effect and loudness estimation. Br J Psychol. 1968 Nov;59(4):385–393. doi: 10.1111/j.2044-8295.1968.tb01153.x. [DOI] [PubMed] [Google Scholar]
  24. Rothenberg S. J., Selkoe D. Specific oculomotor deficit after diazepam. I. Saccadic eye movements. Psychopharmacology (Berl) 1981;74(3):232–236. doi: 10.1007/BF00427100. [DOI] [PubMed] [Google Scholar]
  25. Rothenberg S. J., Selkoe D. Specific oculomotor deficit after diazepam. II. Smooth pursuit eye movements. Psychopharmacology (Berl) 1981;74(3):237–240. doi: 10.1007/BF00427101. [DOI] [PubMed] [Google Scholar]
  26. Rothenberg S., Schottenfeld S., Gross K., Selkoe D. Specific oculomotor deficit after acute methadone. I. Saccadic eye movements. Psychopharmacology (Berl) 1980;67(3):221–227. doi: 10.1007/BF00431260. [DOI] [PubMed] [Google Scholar]
  27. Salonen M., Aaltonen L., Aantaa E., Kanto J. Saccadic eye movements in determination of the residual effects of flunitrazepam. Acta Pharmacol Toxicol (Copenh) 1986 Oct;59(4):303–305. doi: 10.1111/j.1600-0773.1986.tb00173.x. [DOI] [PubMed] [Google Scholar]
  28. Schiller P. H., Sandell J. H., Maunsell J. H. The effect of frontal eye field and superior colliculus lesions on saccadic latencies in the rhesus monkey. J Neurophysiol. 1987 Apr;57(4):1033–1049. doi: 10.1152/jn.1987.57.4.1033. [DOI] [PubMed] [Google Scholar]
  29. Wilkinson I. M. The influence of drugs and alcohol upon human eye movement. Proc R Soc Med. 1976 Jul;69(7):479–480. [PMC free article] [PubMed] [Google Scholar]
  30. Wood C. D., Graybiel A. Evaluation of sixteen anti-motion sickness drugs under controlled laboratory conditions. Aerosp Med. 1968 Dec;39(12):1341–1344. [PubMed] [Google Scholar]

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