Advertisement

Psychopharmacology

, Volume 66, Issue 3, pp 289–290 | Cite as

Self-rated sedation and plasma concentrations of desmethyldiazepam following single doses of clorazepate

  • David J. Greenblatt
  • Richard I. Shader
  • Jerold S. Harmatz
  • Anastasios Georgotas
Original Investigations

Abstract

Plasma concentrations of desmethyldiazepam (DMDZ) and intensity of self-rated sedation (SRS) were measured at multiple points in time during 6h after a single 15 mg oral dose of clorazepate dipotassium. Mean plasma DMDZ levels and mean SRS scores both became maximal at 1.0–2.5 h after drug dosage. By 6 h, however, mean SRS had returned to the predrug baseline score while mean DMDZ concentration fell only slighty from the maximum value. Disappearance of SRS despite persistence of high DMDZ levels might be due to adaptation or tolerance. If this is the case, subjective effects of benzodiazepines may depend upon duration of drug exposure as well as dose and concentration.

Key words

Benzodiazepines Clorazepate Desmethyldiazepam Plasma concentrations Sedation 

References

  1. Cannizzaro, G., Nigito, S., Provenzano, P. M., Vitikova, T.: Modification of depressant and disinhibitory action of flurazepam during short-term treatment in the rat. Psychopharmacologia 26, 173–184 (1972)Google Scholar
  2. Greenblatt, D. J.: Determination of desmethyldiazepam in plasma by electron-capture GLC: Application to pharmacokinetic studies of clorazepate. J. Pharm. Sci. 67, 427–429 (1978)Google Scholar
  3. Greenblatt, D. J., Shader, R. I.: Dependence, tolerance, and addition to benzodiazepines: Clinical and pharmacokinetic considerations. Drug Metab. Rev. 8, 13–28 (1978)Google Scholar
  4. Greenblatt, D. J., Shader, R. I., Harmatz, J. S., Franke, K., Koch-Weser, J.: Absorption rate, blood concentrations, and early responses to oral chlordiazepoxide. Am. J. Psychiatry 134, 559–562 (1977)Google Scholar
  5. Greenblatt D. J., Woo, E., Allen, M. D., Orsulak, P. J., Shader, R. I.: Rapid recovery from massive diazepan overdosage. JAMA 240, 1872–1874 (1978)Google Scholar
  6. Grundstrom R., Holmberg G., Hansen, T.: Degree of sedation obtained with various doses of diazepam and nitrazepam. Acta Pharmacol. Toxicol. (Kbh.) 43, 13–18 (1978)Google Scholar
  7. hillestad, L., Hansten, T., Melsom, H.: Diazepam metabolism in normal man. Serum concentrations and clinical effect after oral administration and cumulation. Clin. Pharmacol. Ther. 16, 485–489 (1974)Google Scholar
  8. MacLeod, S. M., Giles, H. G., Patzalek, G., Thiessen, J. J., Sellers, E. M.: Diazepam actions and plasma concentrations following ethanol ingestion. Eur. J. Clin. Pharmacol. 11, 345–349 (1977)Google Scholar
  9. Margules, D. L., Stein, L.: Increase of “antianxiety” activity and tolerance of behavioral depression during chronic administration of oxazepam. Psychopharmacologia 13, 74–80 (1968)Google Scholar
  10. Matsuki, K., Iwamoto, T.: Development of tolerance to tranquiliziers in the rat. Jpn. J. Pharmacol. 16, 191–197 (1966)Google Scholar
  11. Maxwell, C.: Sensitivity and accuracy of the visual analogue scale. Br. J. Clin. Pharmacol. 6, 15–24 (19678)Google Scholar
  12. Sepinwall, J., Grodsky, F. S., Cook, L.: Conflict behavior in the squirrel monkey: Effect of chlordiazepoxide, diazepam and N-desmethyldiazepam. J. Pharmacol. Exp. Ther. 204 88–102 (1978)Google Scholar
  13. Shader, R. I., Georgotas, A., Greenblatt, D. J., Harmatz, J. S., Allen, M. D.: Impaired absorption of desmethyldiazepam from clorazepate by magnesium aluminium hydroxide. Clin Pharmacol. Ther. 24, 308–315 (1978)Google Scholar
  14. Stein, L., Berger, B. D.: Psychopharmacology of 7-7-chloro-5-(o-7-7-chloro-5-(o-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepan-2-one (Lorazepam) in squirrel monkey and rat. Arzneim. Forsch. 21, 1073–1078 (1971)Google Scholar

Copyright information

© Springer-Verlag 1979

Authors and Affiliations

  • David J. Greenblatt
    • 1
    • 2
  • Richard I. Shader
    • 1
    • 2
  • Jerold S. Harmatz
    • 1
    • 2
  • Anastasios Georgotas
    • 1
    • 2
  1. 1.Clinical Pharmacology UnitMassachusetts General HospitalBostonUSA
  2. 2.Psychopharmacology Research LaboratoryMassachusetts Mental Health CenterBostonUSA

Personalised recommendations