Comparative Pharmacodynamics of Benzodiazepines

  • E. H. EllinwoodJr.
  • A. M. Nikaido
  • D. G. Heatherly
Part of the Psychopharmacology Series book series (PSYCHOPHARM, volume 3)


Dispositional pharmacokinetics have been shown to have little relationship to drug effects after acute doses of certain benzodiazepines (Ellinwood et al. 1983, 1985; Lader 1979; Ziegler et al. 1983). For diazepam the rapid onset of acute tolerance follows the peak behavioral effect; that is, impairment of performance in cognitive-neuromotor tests declines considerably faster than the corresponding serum drug concentration (Ellinwood et al. 1983, 1985). Other studies have described a relatively short period of impairment for high single doses of diazepam (George and Dundee 1977) and a more prolonged period of impairment for lorazepam (Seppala et al. 1976), although the elimination half-lives (t1/2) of diazepam and its active metabolite N-desmethyldiazepam (Mandelli et al. 1978) are over twice as long as that of lorazepam, which has no active metabolites.


Serum Drug Concentration High Single Dose Digit Symbol Substitution Acute Tolerance Receptor Kinetic 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ellinwood EH Jr, Linnoila M, Easier ME, Molter DW (1983) Profile of acute tolerance to three sedative anxiolytics. Psychopharmacology (Berlin) 80: 376–379CrossRefGoogle Scholar
  2. Ellinwood EH Jr, Heatherly DG, Nikaido AM, Bjornsson TD, Kilts C (1985) Comparative pharmacokinetics and pharmacodynamics of lorazepam, alprazolam and diazepam. Psychopharmacology (Berlin) 86: 392–399CrossRefGoogle Scholar
  3. George KA, Dundee JW (1977) Relative amnesic actions of diazepam, flunitrazepam and lorazepam in man. Br J Clin Pharmacol 4: 45–50PubMedGoogle Scholar
  4. Greenblatt DJ, Divoll M, Moschitta LJ, Shader RI (1981) Electron-capture gas chromatographic analysis of the triazolobenzodiazepines alprazolam and triazolam. J Chromatogr 225: 202–207PubMedCrossRefGoogle Scholar
  5. Greenblatt DJ, Divoll M, Abernethy DR, Ochs HR, Shader RI (1983) Clinical pharmacokinetics of the newer benzodiazepines. Clin Pharmacokinet 8: 233–252PubMedCrossRefGoogle Scholar
  6. Iorio LC, Barnett A, Billard W (1984) Selective affinity of 1 -IV-trifluoroethyl benzodiazepines for cerebellum type 1 receptor sites. Life Sci 35: 105–113PubMedCrossRefGoogle Scholar
  7. Lader M (1979) Correlation of plasma concentrations of benzodiazepines with clinical effect. In: Priest RG, Pletscher A, Ward J (eds) Sleep research. MTP Press, LancasterGoogle Scholar
  8. Mandelli M, Tognoni G, Garattini S (1978) Clinical pharmacokinetics of diazepam. Clin Pharmacokinet 3: 72–91Google Scholar
  9. Seppala T, Leino T, Linnoila M, Huttunen M, Ylikahri R (1976) Effects of hangover on psychomotor skills related to driving: modification by fructose and glucose. Acta Pharmacol Toxicol 38: 209–218CrossRefGoogle Scholar
  10. Sieghart W (1983) Several new benzodiazepines selectively interact with a benzodiazepine recep-tor subtype. Neurosci Lett 38: 73–78PubMedCrossRefGoogle Scholar
  11. Sieghart W, Karobarth M (1980) Molceular heterogeneity of benzodiazepine receptors. Nature 286: 285–287PubMedCrossRefGoogle Scholar
  12. Ziegler WH, Schalch E, Leishman B, Eckert M (1983) Comparison of the effect of intravenously administered midazolam and triazolam and their hydroxymetabolites. Br J Clin Pharmacol 16: 63s–69sPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1987

Authors and Affiliations

  • E. H. EllinwoodJr.
  • A. M. Nikaido
    • 1
  • D. G. Heatherly
    • 1
  1. 1.Behavioral Neuropharmacology Section, Department of PsychiatryDuke University Medical CenterDurhamUSA

Personalised recommendations