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British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1981 Oct;12(4):523–533. doi: 10.1111/j.1365-2125.1981.tb01261.x

The relationship between peak velocity of saccadic eye movements and serum benzodiazepine concentration.

P R Bittencourt, P Wade, A T Smith, A Richens
PMCID: PMC1401908  PMID: 6794587

Abstract

1 Six healthy male volunteers received single oral doses of 10 mg diazepam, 20 mg temazepam, 15 mg flurazepam, 5 mg nitrazepam, 10 mg desmethyl-diazepam and placebo in a double-blind randomized fashion. 2 Peak velocity of saccadic eye movements, serum benzodiazepine concentration, and subjective ratings of wakefulness and co-ordination were measured at intervals up to 12 h after drug administration. 3 All active treatments produced a statistically significant decrease in peak saccadic velocity. The effect of temazepam and diazepam was generally more pronounced than that of flurazepam, nitrazepam and desmethyl-diazepam. 4 There were log-linear correlations between peak saccadic velocity and serum benzodiazepine concentration after ingestion of temazepam, diazepam and nitrazepam. 5 These results demonstrate a clear relationship between serum benzodiazepine concentration and its effect on a convenient measure of brainstem reticular formation function.

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Selected References

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  1. ADAMS R. D., VICTOR M., MANCALL E. L. Central pontine myelinolysis: a hitherto undescribed disease occurring in alcoholic and malnourished patients. AMA Arch Neurol Psychiatry. 1959 Feb;81(2):154–172. [PubMed] [Google Scholar]
  2. Aschoff J. C. Veränderungen rascher Blickbewegungen (Saccaden) beim Menschen unter Dizepam (Valium) Arch Psychiatr Nervenkr (1970) 1968;211(4):325–332. doi: 10.1007/BF00404467. [DOI] [PubMed] [Google Scholar]
  3. Baloh R. W., Sills A. W., Kumley W. E., Honrubia V. Quantitative measurement of saccade amplitude, duration, and velocity. Neurology. 1975 Nov;25(11):1065–1070. doi: 10.1212/wnl.25.11.1065. [DOI] [PubMed] [Google Scholar]
  4. Baloh R. W., Yee R. D., Boder E. Eye movements in ataxia-telangiectasia. Neurology. 1978 Nov;28(11):1099–1104. doi: 10.1212/wnl.28.11.1099. [DOI] [PubMed] [Google Scholar]
  5. Becker W., Fuchs A. F. Further properties of the human saccadic system: eye movements and correction saccades with and without visual fixation points. Vision Res. 1969 Oct;9(10):1247–1258. doi: 10.1016/0042-6989(69)90112-6. [DOI] [PubMed] [Google Scholar]
  6. Bellantuono C., Reggi V., Tognoni G., Garattini S. Benzodiazepines: clinical pharmacology and therapeutic use. Drugs. 1980 Mar;19(3):195–219. doi: 10.2165/00003495-198019030-00004. [DOI] [PubMed] [Google Scholar]
  7. Bittencourt P. R., Gresty M. A., Richens A. Quantitative assessment of smooth-pursuit eye movements in healthy and epileptic subjects. J Neurol Neurosurg Psychiatry. 1980 Dec;43(12):1119–1124. doi: 10.1136/jnnp.43.12.1119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bittencourt P., Richens A., Toseland P. A., Wicks J. F., Latham A. N. Pharmacokinetics of the hypnotic benzodiazepine, temazepam. Br J Clin Pharmacol. 1979;8(1):37S–38S. doi: 10.1111/j.1365-2125.1979.tb00453.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bond A. J., Lader M. H. Residual effects of hypnotics. Psychopharmacologia. 1972;25(2):117–132. doi: 10.1007/BF00423189. [DOI] [PubMed] [Google Scholar]
  10. Breimer D. D. Pharmacokinetics and metabolism of various benzodiazepines used as hypnotics. Br J Clin Pharmacol. 1979;8(1):7S–13S. doi: 10.1111/j.1365-2125.1979.tb00449.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Clarke C. H., Nicholson A. N. Immediate and residual effects in man of the metabolites of diazepam. Br J Clin Pharmacol. 1978 Oct;6(4):325–331. doi: 10.1111/j.1365-2125.1978.tb00859.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cummings J. L., Greenberg R. Sleep patterns in the "locked-in" syndrome. Electroencephalogr Clin Neurophysiol. 1977 Aug;43(2):270–271. doi: 10.1016/0013-4694(77)90134-1. [DOI] [PubMed] [Google Scholar]
  13. Feinberg I., Fein G., Walker J. M., Price L. J., Floyd T. C., March J. D. Flurazepam effects on sleep EEG. Visual, computer, and cycle analysis. Arch Gen Psychiatry. 1979 Jan;36(1):95–102. doi: 10.1001/archpsyc.1979.01780010101012. [DOI] [PubMed] [Google Scholar]
  14. Fink M., Weinfeld R. E., Schwartz M. A., Conney A. H. Blood levels and electroencephalographic effects of diazepam and bromazepam. Clin Pharmacol Ther. 1976 Aug;20(2):184–191. doi: 10.1002/cpt1976202184. [DOI] [PubMed] [Google Scholar]
  15. Gentles W., Thomas E. L. Commentary. Effect of benzodiazepines upon saccadic eye movements in man. Clin Pharmacol Ther. 1971 Jul-Aug;12(4):563–574. doi: 10.1002/cpt1971124563. [DOI] [PubMed] [Google Scholar]
  16. Greenblatt D. J., Shader R. I., Koch-Weser J. Flurazepam hydrochloride. Clin Pharmacol Ther. 1975 Jan;17(1):1–14. doi: 10.1002/cpt19751711. [DOI] [PubMed] [Google Scholar]
  17. Greenblatt D. J., Shader R. I., MacLeod S. M., Sellers E. M. Clinical pharmacokinetics of chlordiazepoxide. Clin Pharmacokinet. 1978 Sep-Oct;3(5):381–394. doi: 10.2165/00003088-197803050-00004. [DOI] [PubMed] [Google Scholar]
  18. Gresty M., Trinder E., Leech J. Perception of everyday visual environments during saccadic eye movements. Aviat Space Environ Med. 1976 Sep;47(9):991–992. [PubMed] [Google Scholar]
  19. Hindmarch I. Psychomotor function and psychoactive drugs. Br J Clin Pharmacol. 1980 Sep;10(3):189–209. doi: 10.1111/j.1365-2125.1980.tb01745.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Jones B. E. Elimination of paradoxical sleep by lesions of the pontine gigantocellular tegmental field in the cat. Neurosci Lett. 1979 Aug;13(3):285–293. doi: 10.1016/0304-3940(79)91508-8. [DOI] [PubMed] [Google Scholar]
  21. Jouvet M. Neurophysiology of the states of sleep. Physiol Rev. 1967 Apr;47(2):117–177. doi: 10.1152/physrev.1967.47.2.117. [DOI] [PubMed] [Google Scholar]
  22. Kaplan S. A., Jack M. L., Alexander K., Weinfeld R. E. Pharmacokinetic profile of diazepam in man following single intravenous and oral and chronic oral administrations. J Pharm Sci. 1973 Nov;62(11):1789–1796. doi: 10.1002/jps.2600621111. [DOI] [PubMed] [Google Scholar]
  23. Keller E. L. Participation of medial pontine reticular formation in eye movement generation in monkey. J Neurophysiol. 1974 Mar;37(2):316–332. doi: 10.1152/jn.1974.37.2.316. [DOI] [PubMed] [Google Scholar]
  24. Luschei E. S., Fuchs A. F. Activity of brain stem neurons during eye movements of alert monkeys. J Neurophysiol. 1972 Jul;35(4):445–461. doi: 10.1152/jn.1972.35.4.445. [DOI] [PubMed] [Google Scholar]
  25. Mahon W. A., Inaba T., Stone R. M. Metabolism of flurazepam by the small intestine. Clin Pharmacol Ther. 1977 Aug;22(2):228–233. doi: 10.1002/cpt1977222228. [DOI] [PubMed] [Google Scholar]
  26. Mandelli M., Tognoni G., Garattini S. Clinical pharmacokinetics of diazepam. Clin Pharmacokinet. 1978 Jan-Feb;3(1):72–91. doi: 10.2165/00003088-197803010-00005. [DOI] [PubMed] [Google Scholar]
  27. Markand O. N., Dyken M. L. Sleep abnormalities in patients with brain stem lesions. Neurology. 1976 Aug;26(8):769–776. doi: 10.1212/wnl.26.8.769. [DOI] [PubMed] [Google Scholar]
  28. Nicholson A. N. Visual analogue scales and drug effects in man. Br J Clin Pharmacol. 1978 Jul;6(1):3–4. doi: 10.1111/j.1365-2125.1978.tb01673.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Osorio I., Daroff R. B. Absence of REM and altered NREM sleep in patients with spinocerebellar degeneration and slow saccades. Ann Neurol. 1980 Mar;7(3):277–280. doi: 10.1002/ana.410070312. [DOI] [PubMed] [Google Scholar]
  30. Przybyla A. C., Wang S. C. Locus of central depressant action of diazepam. J Pharmacol Exp Ther. 1968 Oct;163(2):439–447. [PubMed] [Google Scholar]
  31. Shader R. I., Georgotas A., Greenblatt D. J., Harmatz J. S., Allen M. D. Impaired absorption of desmethyldiazepam from clorazepate by magnesium aluminum hydroxide. Clin Pharmacol Ther. 1978 Sep;24(3):308–315. doi: 10.1002/cpt1978243308. [DOI] [PubMed] [Google Scholar]
  32. Simon R. P., Gershon M. D., Brooks D. C. The role of the raphe nuclei in the regulation of ponto-geniculo-occipital wave activity. Brain Res. 1973 Aug 30;58(2):313–330. doi: 10.1016/0006-8993(73)90004-8. [DOI] [PubMed] [Google Scholar]
  33. Skegg D. C., Richards S. M., Doll R. Minor tranquillisers and road accidents. Br Med J. 1979 Apr 7;1(6168):917–919. doi: 10.1136/bmj.1.6168.917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Smith A. T., Bittencourt P. R., Lloyd D. S., Richens A. An efficient technique for determining characteristics of saccadic eye movements using a mini computer. J Biomed Eng. 1981 Jan;3(1):39–43. doi: 10.1016/0141-5425(81)90103-5. [DOI] [PubMed] [Google Scholar]
  35. Solomon F., White C. C., Parron D. L., Mendelson W. B. Sleeping pills, insomnia and medical practice. N Engl J Med. 1979 Apr 5;300(14):803–808. doi: 10.1056/NEJM197904053001423. [DOI] [PubMed] [Google Scholar]
  36. Weber R. B., Daroff R. B. The metrics of horizontal saccadic eye movements in normal humans. Vision Res. 1971 Sep;11(9):921–928. doi: 10.1016/0042-6989(71)90212-4. [DOI] [PubMed] [Google Scholar]
  37. Wittenborn J. R. Effects of benzodiazepines on psychomotor performance. Br J Clin Pharmacol. 1979;7 (Suppl 1):61S–67S. doi: 10.1111/j.1365-2125.1979.tb04667.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. de Silva J. A., Bekersky I., Puglisi C. V., Brooks M. A., Weinfeld R. E. Determination of 1,4-benzodiazepines and -diazepin-2-ones in blood by electron-capture gas-liquid chromatography. Anal Chem. 1976 Jan;48(1):10–19. doi: 10.1021/ac60365a037. [DOI] [PubMed] [Google Scholar]
  39. de Silva J. A., Puglisi C. V., Brooks M. A., Hackman M. R. Determination of flurazepam (Dalmane) and its major metabolites in blood by electron-capture gas-liquid chromatography and in urine by differential pulse polarography. J Chromatogr. 1974 Nov 6;99(0):461–483. doi: 10.1016/s0021-9673(00)90877-x. [DOI] [PubMed] [Google Scholar]

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