Skip to main content
PMC home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1983 May;15(5):545–552. doi: 10.1111/j.1365-2125.1983.tb02088.x

Development of tolerance and cross-tolerance to the psychomotor actions of lorazepam and diazepam in man.

K Aranko, M J Mattila, T Seppälä
PMCID: PMC1427709  PMID: 6134543

Abstract

1 Development of tolerance and cross-tolerance to lorazepam and diazepam in man was assessed in a double-blind and cross-over trial where eight pretrained healthy students volunteered for four 1 week treatment periods started at 1 month intervals. 2 In each period acute psychomotor responses to oral lorazepam 3 mg and diazepam 15 mg were recorded on day 1, as well as on day 8 after 1 week's treatment twice daily with diazepam 5 mg, lorazepam 1 mg, and placebo. At each session several objective psychomotor tests and subjective assessments were done before the drug intake and 1, 2.5, and 4 h after it. 3 In general, the effects of lorazepam were stronger and of longer duration than those of diazepam at the doses used. When comparing the single-dose responses on days 1 and 8, tolerance to lorazepam effects and some cross-tolerance developed on several functions measured. Tolerance but not cross-tolerance developed on choice reaction errors whereas the opposite was found on flicker fusion. No definite tolerance was found on subjective effects. 4 The results tally with an assumption that tolerance to benzodiazepine actions develops at different rates on various parameters measured.

Full text

PDF
545

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Church M. W., Johnson L. C. Mood and performance of poor sleepers during repeated use of flurazepam. Psychopharmacology (Berl) 1979 Mar 28;61(3):309–316. doi: 10.1007/BF00432277. [DOI] [PubMed] [Google Scholar]
  2. Crawley J. N., Marangos P. J., Stivers J., Goodwin F. K. Chronic clonazepam administration induces benzodiazepine receptor subsensitivity. Neuropharmacology. 1982 Jan;21(1):85–89. doi: 10.1016/0028-3908(82)90216-7. [DOI] [PubMed] [Google Scholar]
  3. Elsass P., Hendel J., Hvidberg E. F., Hansen T., Gymoese E., Rathje J. Kinetics and neuropsychologic effects of IV diazepam in the presence and absence of its active N-desmethyl metabolite in humans. Psychopharmacology (Berl) 1980;70(3):307–312. doi: 10.1007/BF00427892. [DOI] [PubMed] [Google Scholar]
  4. File S. E., Bond A. J., Lister R. G. Interaction between effects of caffeine and lorazepam in performance tests and self-ratings. J Clin Psychopharmacol. 1982 Apr;2(2):102–106. [PubMed] [Google Scholar]
  5. File S. E. Rapid development of tolerance to the sedative effects of lorazepam and triazolam in rats. Psychopharmacology (Berl) 1981;73(3):240–245. doi: 10.1007/BF00422410. [DOI] [PubMed] [Google Scholar]
  6. File S. E. Recovery from lorazepam tolerance and the effects of a benzodiazepine antagonist (RO 15-1788) on the development of tolerance. Psychopharmacology (Berl) 1982;77(3):284–288. doi: 10.1007/BF00464581. [DOI] [PubMed] [Google Scholar]
  7. Hannington-Kiff J. G. Measurement of recovery from outpatient general anaesthesia with a simple ocular test. Br Med J. 1970 Jul 18;3(5715):132–135. doi: 10.1136/bmj.3.5715.132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hendel J., Elsass P., Sørensen K. H., Møller I. W., Hvidberg E. F., Hansen T. Anxiety and sedation during a stressful situation after single dose of diazepam versus N-desmethyldiazepam--a controlled trial. Psychopharmacology (Berl) 1980;70(3):303–305. doi: 10.1007/BF00427891. [DOI] [PubMed] [Google Scholar]
  9. Hills M., Armitage P. The two-period cross-over clinical trial. Br J Clin Pharmacol. 1979 Jul;8(1):7–20. doi: 10.1111/j.1365-2125.1979.tb05903.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Klotz U., Reimann I. Clearance of diazepam can be impaired by its major metabolite desmethyldiazepam. Eur J Clin Pharmacol. 1981;21(2):161–163. doi: 10.1007/BF00637518. [DOI] [PubMed] [Google Scholar]
  12. Liljequist R., Mattila M. J. Acute effects of temazepam and nitrazepam on psychomotor skills and memory. Acta Pharmacol Toxicol (Copenh) 1979 May;44(5):364–369. doi: 10.1111/j.1600-0773.1979.tb02346.x. [DOI] [PubMed] [Google Scholar]
  13. Margules D. L., Stein L. Increase of "antianxiety" activity and tolerance of behavioral depression during chronic administration of oxazepam. Psychopharmacologia. 1968;13(1):74–80. doi: 10.1007/BF00401620. [DOI] [PubMed] [Google Scholar]
  14. Mattila M. J., Palva E., Savolainen K. Caffeine antagonizes diazepam effects in man. Med Biol. 1982 Apr;60(2):121–123. [PubMed] [Google Scholar]
  15. Palva E. S., Linnoila M. Effect of active metabolites of chlordiazepoxide and diazepam, alone or in combination with alcohol, on psychomotor skills related to driving. Eur J Clin Pharmacol. 1978 Jul 30;13(5):345–350. doi: 10.1007/BF00644607. [DOI] [PubMed] [Google Scholar]
  16. Rosenberg H. C., Chiu T. H. Tolerance during chronic benzodiazepine treatment associated with decreased receptor binding. Eur J Pharmacol. 1981 Apr 9;70(4):453–460. doi: 10.1016/0014-2999(81)90356-3. [DOI] [PubMed] [Google Scholar]
  17. Savolainen K., Linnavuo M. Effects of m-xylene on human equilibrium measured with a quantitative method. Acta Pharmacol Toxicol (Copenh) 1979 Apr;44(4):315–318. doi: 10.1111/j.1600-0773.1979.tb02336.x. [DOI] [PubMed] [Google Scholar]
  18. Seppälä K., Korttila K., Häkkinen S., Linnoila M. Residual effects and skills related to driving after a single oral administration of diazepam, medazepam or lorazepam. Br J Clin Pharmacol. 1976 Oct;3(5):831–841. doi: 10.1111/j.1365-2125.1976.tb00635.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Seppälä T., Aranko K., Mattila M. J., Shrotriya R. C. Effects of alcohol on buspirone and lorazepam actions. Clin Pharmacol Ther. 1982 Aug;32(2):201–207. doi: 10.1038/clpt.1982.148. [DOI] [PubMed] [Google Scholar]
  20. Seppälä T., Palva E., Mattila M. J., Korttila K., Shrotriya R. C. Tofisopam, a novel 3,4-benzodiazepine: multiple-dose effects on psychomotor skills and memory. Comparison with diazepam and interactions with ethanol. Psychopharmacology (Berl) 1980;69(2):209–218. doi: 10.1007/BF00427652. [DOI] [PubMed] [Google Scholar]
  21. Stubbs D. F. Visual analogue scales. Br J Clin Pharmacol. 1979 Jan;7(1):124–124. doi: 10.1111/j.1365-2125.1979.tb00911.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Young W. S., 3rd, Kuhar M. J. Radiohistochemical localization of benzodiazepine receptors in rat brain. J Pharmacol Exp Ther. 1980 Feb;212(2):337–346. [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES