Skip to main content
SpringerLink
Log in

Pharmacokinetics in the rat of the hallucinogenic alkaloids harmine and harmaline

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

  1. 1.

    After i. v. injection in rats, harmine and harmaline were distributed in the organism within a few seconds. In spite of the close chemical relationship, both alkaloids revealed significant pharmacokinetic differences.

  2. 2.

    Highest concentrations occurred for harmine in the lung and for harmaline in the kidney. The uptake into brain was for harmaline slower than for harmine. The rate of elimination was in general smaller for harmaline than for harmine.

  3. 3.

    Harmaline was excreted into chymus and urine to a greater extent than harmine.

  4. 4.

    The binding to proteins of rat plasma was 94.5% for harmine and 52% for harmaline. Concentrations of free drug in plasma water were used to assess the binding to various tissues.

  5. 5.

    The extent of tissue binding and the rate of its development were different for both drugs.

  6. 6.

    The duration of tremor and the strength and decline of bradycardia were determined to compare the distribution of the drugs with their effects.

  7. 7.

    The drug concentration (in brain and heart) at the termination of the effect (tremor and bradycadia) was used as a parameter connecting the pharmacokinetic and the pharmacodynamic events.

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

References

  • Bosin, T. R., Campaigne, E., Maickel, R. P.: Biochemical pharmacology of benzo (b)thiophene analogs of harmaline and harmine. Life Sci. 11, 685–691 (1972)

    Google Scholar 

  • Brodie, B. B., Hogben, C. A. M.: Some physico-chemical factors in drug action. J. Pharm. Pharmacol. 9, 345–380 (1957)

    Google Scholar 

  • Cohen, Y.: Binding of drugs to plasma and tissue proteins. In: International Encyclopedia of Pharmacology and Therapeutics. Section 78, Vol. I, Cohen, Y. (Ed.), Radionuclides in Pharmacology, pp. 241–273, Oxford, New York, Toronto, Sydney, Braunschweig: Pergamon Press, 1971

    Google Scholar 

  • Dost, F. H.: Grundlagen der Pharmakokinetik, 2. Aufl. Stuttgart: Thieme 1968

    Google Scholar 

  • Eichelbaum, M., Hengstmann, J. H., Dengler, H. J.: Das Verteilungsmuster des Chlorphentermins bei Ratte, Kaninchen und Schwein. Naunyn-Schmiedeberg's Arch. Pharmak. 267, 446–456 (1970)

    Google Scholar 

  • Gibaldi, M., Nagashima, R., Levy, G.: Relationship between drug concentration in plasma or serum and amount of drug in the body. J. pharm. Sci. 58, 193–197 (1969)

    Google Scholar 

  • Gillette, J. R.: Overview of drug-protein binding. Ann. N. Y. Acad. Sci. 226, 6–17 (1973)

    Google Scholar 

  • Ho, B. T., Estevez, V., Fritchie, G. E., Tansey, L. W., Idänpään-Heikkilä, J., McIsaac, W. M.: Metabolism of harmaline in rats. Biochem. Pharmacol. 20, 1313–1319 (1971)

    Google Scholar 

  • Hoffer, A., Osmond, H.: The Hallucinogens. New York: Academic Press Inc. 1967

    Google Scholar 

  • Jähnchen, E., Krieglstein, J., Kunkel, F., Samuelis, W. J., Wollert, U.: Die Bedeutung der Bindung von Pharmaka an Albumin und Erythrocyten eines Perfusionsmediums der isolierten Rattenleber. Naunyn-Schmiedebergs Arch. Pharmak. 269, 67–84 (1971)

    Google Scholar 

  • Jusko, W. J., Gibaldi, M.: Effects of change in elimination on various parameters of the two-compartment open model. J. pharm. Sci. 61, 1270–1273 (1972)

    Google Scholar 

  • Jusko, W. J., Lewis, G. P., Dittert, L. W.: Integral coefficients of multi-compartment pharmacokinetic models. Application to chemotherapy. Chemotherapy 17, 109–120 (1972)

    Google Scholar 

  • Keen, P.: Effect of binding to plasma proteins on the distribution, activity and elimination of drugs. In: Handbuch der experimentellen Pharmakologie. Eichler, O., Farah, A., Herken, H., Welch, A. D. (Eds.), Vol. XXVIII/1: Concepts in Biochemical Pharmacology. Brodie, B. B., Gillette, J. R., Ackerman, H. S. (Eds.), pp. 213–233. Berlin-Heidelberg-New York: Springer 1971

    Google Scholar 

  • Kolassa, N., Pfleger, K.: Bindung von Hexobendin an Plasmaproteine und Erythrocyten bei Mensch, Hund und Ratte. Arch. int. Pharmacodyn. 203, 46–54 (1973)

    Google Scholar 

  • Krieglstein, J.: Bestimmungsmethoden, physikochemische Grundlagen und pharmakokinetische Bedeutung der Plasmaproteinbindung von Arzneimitteln. Arzneimittel-Forsch. 23, 1527–1529 (1973a)

    Google Scholar 

  • Krieglstein, J.: Die Bedeutung der Lipophilie von Arzneimitteln für deren Verteilung im Organismus. Dtsch. med. Wschr. 98, 1509–1510 (1973b)

    Google Scholar 

  • Krieglstein, J., Kuschinsky, G.: Über die Wechselwirkung von Phenothiazinderivaten mit Rinderserumalbumin. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. 262, 1–16 (1969)

    Google Scholar 

  • Krüger-Thiemer, E.: Application of kinetic analysis for calculation of dosage regimens. In: Siegler, P. E., Moyer, J. H. (Eds.): Animal and Clinical Pharmacologic Techniques in Drug Evaluation, Vol. 2, pp. 217–238, Chicago: Year Book Medical Publishers Inc. 1967

    Google Scholar 

  • Kurz, H.: Die Bedeutung der Lipoidlöslichkeit in der Pharmakologie. Präparat. Pharmaz. 6, 1–12 (1970)

    Google Scholar 

  • Levy, G.: Kinetics of pharmacologic effects. Clin. Pharmacol. Ther. 7, 362–372 (1966)

    Google Scholar 

  • Lüllmann, H., Peters, T., van Zwieten, P. A.: The distribution of 3H-labelled cardenolides between isolated guinea-pig atrial tissue and circulating, oxygenated whole blood. Brit. J. Pharmacol. 36, 276–285 (1969)

    Google Scholar 

  • Martin, B. K.: Potential effect of the plasma proteins on drug distribution. Nature (Lond.) 207, 274–276 (1965)

    Google Scholar 

  • Naranjo, C.: Psychotropic properties of the harmala alkaloids. In: Ethnopharmacologic Search for Psychoactive Drugs. Efron, D. H., Holmstedt, B., Kline, N.S. (Eds.), pp. 385–391. Public Health Service Publication No. 1645, Washington 1967

  • Oldendorf, W. H.: Blood-brain barrier premeability to drugs. Ann. Rev. Pharmacol. 14, 239–248 (1974)

    Google Scholar 

  • Oldendorf, W. H., Hyman, S., Braun, L., Oldendorf, S. Z.: Blood-brain barrier: Penetration of morphine, codeine, heroin, and methadone after carotid injection. Science 178, 984–985 (1972)

    Google Scholar 

  • Raaflaub, J.: Über die Beziehungen zwischen der Lipidlöslichkeit von Pharmaka und ihrem pharmakokinetischen Verhalten. Experientia (Basel) 26, 457–467 (1970)

    Google Scholar 

  • Riegelman, S., Loo, J. C. K., Rowland, M.: Shortcomings in pharmacokinetic analysis by conceiving the body to exhibit properties of a single compartment. J. pharm. Sci. 57, 117–123 (1968a)

    Google Scholar 

  • Riegelman, S., Loo, J., Rowland, M.: Concept of a volume of distribution and possible errors in evaluation of this parameter. J. pharm. Sci. 57, 128–133 (1968b)

    Google Scholar 

  • Riggs, D. S.: The mathematical approach to physiological problems, pp. 146–161. Cambridge-London: M. I. T. Press, 1972

    Google Scholar 

  • Schultes, R. E.: Hallucinogens of plant origin. Science 163, 245–254 (1969)

    Google Scholar 

  • Slotkin, T. A., DiStefano, V., Au, W. Y. W.: Blood levels and urinary excretion of harmine and its metabolites in man and rats. J. Pharmacol. exp. Ther. 173, 26–30 (1970)

    Google Scholar 

  • Strubelt, O., Back, G., Uhl, E., Zetler, G.: Cardiac output, heart rate, and blood pressure as influenced by equi-antiarrhythmic doses of eight antifibrillatory agents. Naunyn-Schmiedebergs Arch. Pharmak. 271, 346–360 (1971)

    Google Scholar 

  • Villeneuve, A., Sourkes, T. L.: Metabolism of harmaline and harmine in the rat. Rev. canad. Biol. 25, 231–239 (1966)

    Google Scholar 

  • Wang, L.: Plasma volume, cell volume, total blood volume and F cells factor in the normal and splenectomized Sherman rat. Amer. J. Physiol. 196, 188–192 (1959)

    Google Scholar 

  • Wassermann, O.: Studies on the pharmacokinetics of bisquaternary ammonium compounds. I. Synthesis, physico-chemical properties and protein-binding of 3H-labelled hexamethonium and of some of its derivatives. Arzneimittel-Forsch. 22, 1993–1995 (1972)

    Google Scholar 

  • Zaharko, D. S., Dedrick, R. L.: Applications of pharmacokinetics to cancer chemotherapy. In: Pharmacology and the Future of Man. Proc. 5th Int. Congr. Pharmacology, San Francisco 1972, Vol. 3, pp. 316–331. Basel: Karger 1973

    Google Scholar 

  • Zetler, G.: Indirect cardiac effects of indole, simple indole derivatives, and harmine. Naunyn-Schmiedebergs Arch. Pharmacol. 283, 165–179 (1974)

    Google Scholar 

  • Zetler, G., Singbartl, G., Schlosser, L.: Cerebral pharmacokinetics of tremor-producing harmala and iboga alkaloids. Pharmacology 7, 237–248 (1972)

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut für Pharmakologie der Medizinischen Hochschule, Ratzeburger Allee 160, D-2400, Lübeck, Federal Republic of Germany

    G. Zetler, G. Back & H. Iven

Authors
  1. G. Zetler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. Back
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. Iven
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zetler, G., Back, G. & Iven, H. Pharmacokinetics in the rat of the hallucinogenic alkaloids harmine and harmaline. Naunyn-Schmiedeberg's Arch. Pharmacol. 285, 273–292 (1974). https://doi.org/10.1007/BF00498996

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00498996

Key words

Search

Navigation