Psychopharmacology

, Volume 79, Issue 2–3, pp 137–141 | Cite as

Profile of acute tolerance to three sedative anxiolytics

  • Everett H. EllinwoodJr.
  • Markku Linnoila
  • Martha E. Easler
  • David W. Molter
Original Investigations

Abstract

Acute tolerance, defined as a decreasing drug effect relative to drug-plasma levels (DPL) over a period of minutes to a few hours, is pronounced following single doses of diazepam or pentobarbital. Both of these lipid-soluble drugs produce an early peak behavioral impairment and subsequent rapid recovery component that is followed by a much slower blood-drug rise time. These pronounced early peak effects were not shared by alcohol, and contribute significantly to the lack of correlation between impairment and DPL.

Key words

Acute tolerance Peak impairment Sedative anxiolytics Plasma concentration 

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References

  1. Bliding A (1974) Effects of different rates of absorption of two benzodiazepines on subjective and objective parameters. Eur J Clin Pharmacol 7:201–211Google Scholar
  2. Brodie BB, Burns JJ, Mark LC, Lief PA, Bernstein E, Papper EM (1953) The fate of pentobarbital in man and dog and a method for its estimation in biological material. J Pharmacol Exp Ther 109:26–34Google Scholar
  3. Clayton AB (1980) Effects of alcohol on driving skills. In: Sandler M (ed) Psychopharmacology of alcohol. Raven, New York, pp 73–78Google Scholar
  4. Crone C (1965) The permeability of the brain capillaries due to nonelectrolites. Acta Physiol Scand 64:407–417Google Scholar
  5. Curry SH, Norris H (1970) Acute tolerance to a sedative in man. Br J Pharmacol 38:450–451Google Scholar
  6. Ellinwood Jr EH, Linnoila M, Angle HV, Moore JW, Skinner JT, Molter DW (1980) Use of simple tasks to test for impairment of complex skills by a sedative. Psychopharmacology 73:350–354Google Scholar
  7. Fischer E, Wallgren H (1957) Cerebral blood flow and cerebral alcohol uptake of anaesthetized dogs. Physiologist 1:27–28Google Scholar
  8. Franks HM, Hensley VA, Khensley WJ, Starmer GA, Teo RKC (1976) The relationship between alcohol dosage and performance decrement in humans. J Stud Alcohol 37:284–297Google Scholar
  9. Grizzle JE, Allen DM (1969) Analysis of growth and dose-response curves. Biometrics 25:357–381Google Scholar
  10. Hurst PM, Bagley SA (1972) Acute adaptation to the effects of alcohol. Q J Stud Alcohol 33:358–378Google Scholar
  11. Jones BM, Vega A (1972) Cognitive performance measured on the ascending and descending limb of the blood alcohol curve. Psychopharmacology 23:99–114Google Scholar
  12. Kalant H (1978) Behavioral criteria for tolerance and physical dependence. In: Fishman J (ed) The bases of addition. Dahlem Konferenzen, Berlin, pp 199–220Google Scholar
  13. Kalant H, LeBlanc AE, Gibbons RJ (1971) Tolerance to, and dependence on some non-opiate psychotropic drugs. Pharmacol Rev 23:135–191Google Scholar
  14. Leeb-Lundberg F, Snowman A, Olsen RW (1980) Barbiturate receptor sites are coupled to benzodiazepine receptors. Proc Natl Acad Sci USA 77:7468–7472Google Scholar
  15. Linnoila M, Dorrity F (1977) Rapid gas-chromatographic assay of serum diazepam, N-desmethyldiazepam, and N-desalkylflurazepam. Acta Pharmacol Toxicol (Copenh) 41:458–464Google Scholar
  16. MacLeod SM, Giles HG, Patzalek G, Thiessen JJ, Sellers EM (1977) Diazepam actions and plasma concentrations following ethanol ingestion. Eur J Clin Pharmacol 11:345–349Google Scholar
  17. Mark LC, Burns JJ, Brand L, Campomanes CI, Trousof N, Papper EM, Brodie BB (1958) The passage of thiobarbiturates and their oxygen analogs into brain. J Pharmacol Exp Ther 123:70–73Google Scholar
  18. Maynert EW, Klingman GI (1960) Acute tolerance to intravenous anesthetics in dogs. J Pharmacol Exp Ther 128:192–200Google Scholar
  19. Mellanby E (1919) Alcohol: Its absorption into and disappearance from the blood under different conditions. G B Med Res Council Spec Rep Ser 31:1–48Google Scholar
  20. Morrison DF (1976) Multivariate statistical methods. McGraw Hill, New York, pp 128–169Google Scholar
  21. Palva ES, Linnoila M (1978) Effect of active metabolites of chlordiazepoxide and diazepam, alone or in combination with alcohol, on psychomotor skills related to driving. Eur J Clin Pharmacol 13:345–350Google Scholar
  22. Paul SM, Marangos PJ, Skolnick P (1981) The benzodiazepine-GABA-chloride ionophere receptor complex: Common site of minor tranquilizer action. Biol Psychiatry 16:213–229Google Scholar
  23. Paul SM, Skolnick P (1978) Rapid changes in brain benzodiazepine receptors after experimental seizures. Science 202:892–893Google Scholar
  24. Reggiani A, Barbaccia ML, Spano PF, Trabucchi M (1980) Acute and chronic ethanol administration of specific 3H-GABA binding in different rat brain areas. Psychopharmacology 67:261–264Google Scholar
  25. Sellers EM (1978) Additive drugs: Dispositional tolerance and dependence interrelationships. Drug Metab Rev 8:5–11Google Scholar
  26. Spirt MM, Bautz G, Zanko M, Horst WD, O'Brien RA (1981) Comparative receptor binding effects in brain after IV lorazepam and diazepam. Neurosci Abstr 7:865Google Scholar
  27. US Department of Transportation (1981) Marijuana and other drugs and their relationship to highway safety: A report to congress. US Government Printing Office, Washington, USAGoogle Scholar
  28. Wahlstrom G, Widerlov E (1971) Interaction and acute cross tolerance between ethanol and hexobarbitone in the rat. J Pharm Pharmacol 23:58–60Google Scholar
  29. Wilkinson PK, Sedman AJ, Sakmar E, Kay DR, Wagner JG (1977) Pharmacokinetics of ethanol after oral administration in the fasting state. J Pharmacokinet Biopharm 5:207–224Google Scholar

Copyright information

© Springer-Verlag 1983

Authors and Affiliations

  • Everett H. EllinwoodJr.
    • 1
  • Markku Linnoila
    • 1
  • Martha E. Easler
    • 1
  • David W. Molter
    • 1
  1. 1.Behavioral Neuropharmacology Section, Department of PsychiatryDuke University Medical CenterNCDurhamUSA

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