Skip to main content
SpringerLink
Log in

Experimentelle und biometrische Untersuchungen über den Zusammenhang von Gehirnkonzentration, Eliminationsgeschwindigkeit, Schlafzeit und Körpertemperatur bei der Hexobarbitalnarkose der Maus

  • Published:
Naunyn-Schmiedebergs Archiv für experimentelle Pathologie und Pharmakologie Aims and scope Submit manuscript

Summary

The hexobarbital concentration in the brain of mice in relation to sleeping time, velocity of elimination and body temperature was studied:

1. When the hexobarbital dose was plotted against the sleeping time at room temperature (both in logarithmic scale) a straight line was obtained. A change in elimination constant or sensitivity produced a parallel shifting of this line.

2. The hexobarbital concentration in brain (logarithmic scale) plotted against time (linear scale) gave a straight line at 37°C and a curve (2nd degree) at 21°C environmental temperature.

3. Sleeping time, hexobarbital concentration in brain at awakening, elimination constant and liver weight were distributed lognormally.

4. At 21°C the sleeping time was longer and the hexobarbital concentration in brain at awakening lower compared with the results obtained at 37°C.

5. After increasing hexobarbital doses at 37°C a higher and at 21°C a lower hexobarbital concentration in brain at awakening were observed. This effect can be due to a change in sensitivity.

6. At room temperature there was a fall of body temperature under hexobarbital anesthesia, followed by a slight rise without reaching the level at beginning. The fall of temperature during the first 90 minutes is explained by physical temperature loss.

7. A pretreatment with chlorpromazine prolonged the hexobarbital sleeping time at 37°C. The lowered hexobarbital concentration in brain at awakening is probably due to a higher sensitivity against hexobarbital.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Literatur

  • Aitchison, J., and I. A. C. Brown: The lognormal distribution. Cambridge: University Press 1957.

    Google Scholar 

  • Block, W., u. I. Ebigt: Zum Stoffwechsel radioaktiv markierter Barbiturate und Thiobarbiturate 5. Beruht die kurze Narkosewirkung der Thiobarbiturate auf ihrer bevorzugten Speicherung im Körperfett? Arzneimittel-Forsch. 11, 59–62 (1961).

    Google Scholar 

  • Borzelleca, J. F., and R. W. Manthei: Factors influencing pentobarbital sleeping time in mice. Arch. int. Pharmacodyn. 111, 296–307 (1957).

    Google Scholar 

  • Brilmayer, H., u. S. J. Loennecken: Die Eliminationsgeschwindigkeit von Barbiturat aus dem Blut akut intoxizierter Patienten. Arch. int. Pharmacodyn. 136, 137–146 (1962).

    Google Scholar 

  • Brodie, B. B., E. Bernstein, and L. C. Mark: The role of body fat in limiting the duration of action of thiopental. J. Pharmacol. exp. Ther. 105, 421–426 (1952).

    Google Scholar 

  • —, P. A. Lief, E. Bernstein, and E. M. Papper: The fate of pentobarbital in man and dog and a method for its estimation in biological material. J. Pharmacol. exp. Ther. 109, 26–34 (1953).

    Google Scholar 

  • —: Some physico-chemical factors in drug action. J. Pharm. Pharmacol. 9, 345–380 (1957).

    Google Scholar 

  • —: Acute tolerance to thiopental. J. Pharmacol. exp. Ther. 102, 215–218 (1951).

    Google Scholar 

  • —, P. A. Lief, E. Bernstein, and E. A. Rovenstine: The fate of thiopental in man and a method for its estimation in biological material. J. Pharmacol. exp. Ther. 98, 85–96 (1950).

    Google Scholar 

  • Brown, A. M.: Sleeping time response of mice — random bred, inbred and F1 hybrids — to pentobarbitone sodium. J. Pharm. Pharmacol. 13, 679–687 (1961).

    Google Scholar 

  • Clark, A. J.: General Pharmacology in Handbuch der experimentellen Pharmakologie, Ergänzungswerk Bd. 4. Berlin: Springer 1937.

    Google Scholar 

  • Cooper, J. R., and B. B. Brodie: Enzyme systems involved in the biotransformation of barbiturates evipal, nembutal, thiopental, secobarbital. J. Pharmacol. exp. Ther. 110, 12 (1954).

    Google Scholar 

  • — The enzymatic metabolism of hexobarbital (evipal). J. Pharmacol. exp. Ther. 114, 409–417 (1955).

    Google Scholar 

  • Dost, F. H.: Der Blutspiegel. Leipzig: Thieme 1953.

    Google Scholar 

  • Dundee, J. W., H. L. Price, and R. D. Dripps: Acute tolerance to thiopentone in man. Brit. J. Anaesth. 28, 344–352 (1956).

    Google Scholar 

  • Fastier, F. N., R. N. Speden, and H. Waal: Prolongation of chloral hydrate sleeping time by 5-hydroxytryptamine and by certain other drugs. Brit. J. Pharmacol. 12, 251–256 (1957).

    Google Scholar 

  • Fisher, R. A.: Statistische Methoden für die Wissenschaft. Edinburgh, London: Oliver and Boyd 1956.

    Google Scholar 

  • Fuhrman, F. A.: The effect of body temperature on drug action. Physiol. Rev. 26, 247–274 (1946).

    Google Scholar 

  • — The effect of body temperature on the duration of barbiturate anaesthesia in mice. Science 105, 387–388 (1947).

    Google Scholar 

  • Fuhrman, G. J., and F. A. Fuhrman: Effects of temperature on the action of drugs. Ann. Rev. Pharmacol. 1, 65–78 (1961).

    Google Scholar 

  • Gaddum, J. H.: Lognormal distribution. Nature (Lond.) 156, 463–466 (1945).

    Google Scholar 

  • Kato, R., E. Chiesara, and P. Vassanelli: The in vitro inhibition of pentobarbital metabolism by chlorpromazine. Experientia (Basel) 18, 269–270 (1962).

    Google Scholar 

  • Komlos, E., u. L. Foldes: Über die Wirkung der Außentemperatur auf die Potenzierung der Evipan-Narkose und die motorische Wirkung des Amphetamins bei weißen Ratten. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 236, 335–342 (1959).

    Google Scholar 

  • Krüger-Thiemer, E., u. B. Schlender: Die Lösung chemotherapeutischer Probleme durch programmgesteuerte Ziffernrechenautomaten. 2. Die exakte Berechnung der Gleichungsparameter und ihrer Vertrauensgrenzen mit Hilfe des Gauß-Newton-Iterationsverfahrens. Arzneimittel-Forsch. 13, 891–894 (1963).

    Google Scholar 

  • Lessin, A. W., and M. W. Parkes: The relation between sedation and body temperature in the mouse. Brit. J. Pharmacol. 12, 245–250 (1957).

    Google Scholar 

  • Ludwig, W., R. Wartmann u. R. Wette: Ein statistisches Problem in Theorie und Praxis. Mittbl. f. math. Statist. 4, 231–242 (1952).

    Google Scholar 

  • Maynert, E. W., and G. J. Klingman: Acute tolerance to intravenous anaesthetics in dogs. J. Pharmacol. exp. Ther. 128, 192–200 (1960).

    Google Scholar 

  • Morris, R. W.: Species differences in the effect of ambient temperature on barbiturate induced sleep. Arch. int. Pharmacodyn. 141, 584–590 (1963a).

    Google Scholar 

  • — Species differences in the effect of body weight on pentobarbital induced sleep. Arch. int. Pharmacodyn. 142, 550–555 (1963b).

    Google Scholar 

  • Netter, H.: Theoretische Biochemie. Berlin, Göttingen, Heidelberg: Springer 1959.

    Google Scholar 

  • Quinn, G. P., J. Axelrod, and B. B. Brodie: Species, strain and sex differences in the metabolism of hexobarbitone, amidopyrine, antipyrine and aniline. Biochem. Pharmacol. 1, 152–159 (1958).

    Google Scholar 

  • Raventos, J.: The influence of room temperature on the action of barbiturates. J. Pharmacol. exp. Ther. 64, 355–363 (1938).

    Google Scholar 

  • Remmer, H.: Geschlechtsspezifische Unterschiede in der Entgiftung von Evipan und Thiopental bei Ratten. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 233, 173–183 (1958a).

    Google Scholar 

  • — Die Wirkungsweise von Hexobarbital und Thiopental in der Kurznarkose. Anaesthesist 7, 97–100 (1958b).

    Google Scholar 

  • — Die Beschleunigung der Evipanoxydation und der Demethylierung von Methylaminoantipyrin durch Barbiturate. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 237, 296–307 (1959).

    Google Scholar 

  • —: Die Gewöhnung an langwirkende Barbiturate. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 243, 468–478 (1962).

    Google Scholar 

  • Rümke, Chr. L., u. J. Bout: Beeinflussung der Wirkung von Pharmaka durch 1–2 Tage vorher gegebene Stoffe. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 241, 152–153 (1961).

    Google Scholar 

  • — R. van Strik, H. de Jonge, and A. Delver: Experiments on the duration of hexobarbital narcosis in mice. Arch. int. Pharmacodyn. 146, 10–26 (1963).

    Google Scholar 

  • Schultz, H.: The standard error of a forecast from a curve. J. Amer. statist. Ass. 25, 139–185 (1930).

    Google Scholar 

  • Setnikar, I., and O. Temelcou: Effect of temperature on toxicity and distribution of pentobarbital and barbital in rats and dogs. J. Pharmacol. exp. Ther. 135, 213–222 (1962).

    Google Scholar 

  • Shideman, F. E., Th. C. Gould, W. D. Winters, R. C. Peterson, and K. W. Warren: The distribution and in vivo rate of metabolism of thiopental. J. Pharmacol. exp. Ther. 107, 368–378 (1953).

    Google Scholar 

  • Spector, W. S.: Handbook of biological data, Philadelphia, London: Saunders 1956.

    Google Scholar 

  • Usinger, W.: Respiratorischer Stoffwechsel und Körpertemperatur der weißen Maus in Narkose und unter Chlorpromazin. Pflügers Arch. ges. Physiol. 265, 365–381 (1957).

    Google Scholar 

  • Wald, A.: The fitting of straight lines if both variables are subject to error. Ann. math. Statist. 11, 284–300 (1940).

    Google Scholar 

  • Weber, E.: Grundriß der biologischen Statistik, 4. Aufl. Jena: G. Fischer 1961.

    Google Scholar 

  • Westphal, W. H.: Physik. Ein Lehrbuch, 18./19. Aufl. Berlin, Göttingen, Heidelberg: Springer 1956.

    Google Scholar 

  • Wette, R.: Regressions- und Kausalanalyse in der Biologie. Metrika 2, 131–137 (1959).

    Google Scholar 

  • Winne, D.: Die Wirkung einiger Schlaf- und Narkosemittel bei röntgenbestrahlten Mäusen. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 243, 212–231 (1962a).

    Google Scholar 

  • — Der Abbau von Hexobarbital in vivo bei ganzkörperbestrahlten Mäusen. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 243, 546–553 (1962b).

    Google Scholar 

  • — Die zwangläufige Korrelation als Ursache von Fehlschlüssen. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 246, 48 (1963).

    Google Scholar 

  • — Die Berechnung einer nichtlinearen Regression. erläutert an einem pharmakologischen Beispiel. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 247, 267–277 (1964).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Aus dem Pharmakologischen Institut der Universität Tübingen, Germany

    D. Winne

Authors
  1. D. Winne
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Mit 3 Textabbildungen

Mit Unterstützung der Deutschen Forschungsgemeinschaft.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Winne, D. Experimentelle und biometrische Untersuchungen über den Zusammenhang von Gehirnkonzentration, Eliminationsgeschwindigkeit, Schlafzeit und Körpertemperatur bei der Hexobarbitalnarkose der Maus. Naunyn - Schmiedebergs Arch 247, 278–294 (1964). https://doi.org/10.1007/BF00245970

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00245970

Search

Navigation