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Indirect cardiac effects of indole, simple indole derivatives, and harmine

  • G. Zetler
Article

Summary

  1. 1.

    Indole, 3-methylindole, 5-methylindole, 5-hydroxyindole, 6-methoxyindole, and harmine produced positive inotropic effects in isolated left guinea-pig atria electrically driven at 1/sec.

     
  2. 2.

    These actions were antagonized by propranolol and pretreatment with reserpine. In atria of reserpine-pretreated animals, treatment with noradrenaline restored only the effects of tyramine, 3-methylindole, and 5-hydroxyindole. Cocaine reduced the effects of tyramine, 3-methylindole, 5-hydroxyindole, and harmine. Hexamethonium antagonized only the effects of 5-hydroxyindole, 6-methoxyindole, and harmine.

     
  3. 3.

    Tachyphylaxis developed more quickly for the indoles than for tyramine. Repletion of noradrenaline stores abolished the tachyphylaxis for 5-hydroxyindole, 6-methoxyindole, and harmine but not for indole, 3-methylindole, and 5-methylindole.

     
  4. 4.

    When the rate of stimulation was increased from 1/sec to 3/sec, the rate of approach to a steady-state response was unaltered for 5-hydroxyindole, decreased for 3-methylindole and harmine, and increased for tyrmaine, indole, 5-methylindole, and 6-methoxyindole. However, the effect of harmine was now negative inotropic.

     
  5. 5.

    It is concluded that these indole derivatives stimulate the heart muscle by releasing noradrenaline, but their properties differ from those of tyramine.

     

Key words

Cardiac Effects Harmine Indole Compounds Half Time of Drug Effect Tachyphylaxis 

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References

  1. Barnett, A., Benforado, J. M.: The nicotine effects of choline esters and of nicotine in guinea pig atria. J. Pharmacol. exp. Ther. 152, 29–36 (1966)Google Scholar
  2. Benfey, B. G., Varma, D. R.: Antisympathomimetic and antifibrillatory effects of pronethalol and propranolol. Brit. J. Pharmacol. 26, 3–8 (1966)Google Scholar
  3. Bhagat, B.: Response of isolated guinea-pig atria to various ganglion-stimulating agents. J. Pharmacol. exp. Ther. 154, 264–270 (1966)Google Scholar
  4. Brown, B. R., Crout, J. R.: The sympathomimetic effect of gallamine on the heart. J. Pharmacol. exp. Ther. 172, 266–273 (1970)Google Scholar
  5. Furchgott, R. F., Kirkepar, S. M., Rieker, M., Schwab, A.: Actions and interactions of norepinephrine, tyramine and cocaine on aortic strips of rabbit and left atria of guinea-pig and cat. J. Pharmacol. exp. Ther. 142, 39–58 (1963)Google Scholar
  6. Geigy, J. R.: Documenta Geigy, Wissenschaftliche Tabellen, 7. Aufl. Basel 1968Google Scholar
  7. Higgins, C.B., Vatner, S. F., Braunwald, E.: Parasympathetic control of the heart. Pharmacol. Rev. 25, 119–155 (1973)Google Scholar
  8. Katzung, B., Rosin, H., Scheider, F.: Frequency-force relationship in the rabbit auricle and its modification by some metabolic inhibitors. J. Pharmacol. exp. Ther. 120, 324–333 (1957)Google Scholar
  9. Kennedy, B. L., West, T. C.: Factors influencing quinidine-induced changes in excitability and contractility. J. Pharmacol. exp. Ther. 168, 47–59 (1969)Google Scholar
  10. Koch-Weser, J.: Myocardial contraction frequency and onset of cardiac glycoside action. Circulat. Res. 28, 34–48 (1971)Google Scholar
  11. Koch-Weser, J., Blinks, J. R.: The influence of the interval between beats on myocardial contractility. Pharmacol. Rev. 15, 601–652 (1963)Google Scholar
  12. Kottegoda, S. R.: Stimulation of isolated rabbit auricles by substances which stimulate ganglia. Brit. J. Pharmacol. 8, 83–86 (1953)Google Scholar
  13. Langer, S.Z., Trendelenburg, U.: The effect of a saturable uptake mechanism on the slopes of dose-response curves for sympathomimetic amines and on the shifts of dose-response curves produced by a competitive antagonist. J. Pharmacol. exp. Ther. 167, 117–142 (1969)Google Scholar
  14. Lee, F.-L., Weiner, N., Trendelenburg, U.: The uptake of tyramine and formation of octopamine in normal and tachyphylactic rat atria. J. Pharmacol. exp. Ther. 155, 211–222 (1967)Google Scholar
  15. Lindmar, R.: Die Wirkung von 1,1-Dimethyl-4-Phenyl-Piperazinium-Jodid am isolierten Vorhof im Vergleich zur Tyramin- und Nicotinwirkung. Naunyn-Schmiedeberg's Arch. exp. Path. Pharmak. 242, 458–466 (1962)Google Scholar
  16. Lindmar, R., Muscholl, E.: Die Wirkung von Cocain, Guanethidin, Reserpin, Hexamethonium, Tetracyin und Psicain auf die Noradrenalin-Freisetzung aus dem Herzen. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 242, 214–227 (1961)Google Scholar
  17. Lüllmann, H., Ziegler, A.: A transient state concept of drug receptor interaction. Naunyn-Schmiedeberg's Arch. Pharmacol. 280, 1–21 (1973)Google Scholar
  18. McNeill, J. H., Brody, T. M.: The effect of various drug pretreatments on amine-induced phosphorylase activation and amine uptake. J. Pharmacol. exp. Ther. 162, 121–133 (1968)Google Scholar
  19. Muscholl, E.: Cholinomimetic drugs and release of the adrenergic transmitter. In: New aspects of storage and release mechanisms of catecholamines. Eds.: H. J. Schümann and G. Kroneberg, pp. 168–186. Berlin-Heidelberg-New York: Springer 1970Google Scholar
  20. Peach, M. J., Chiu, A. T.: The influence of acidosis on the chronotropic effects of tyramine in guinea-pig atria: Relation to tyramine uptake and metabolism. J. Pharmacol. exp. Ther. 183, 73–79 (1972)Google Scholar
  21. Ross, S. B., Renyi, A. L.: Uptake and metabolism of β-phenethylamine and tyramine in mouse brain and heart slices. J. Pharm. Pharmacol. 23, 276–279 (1971)Google Scholar
  22. Singbartl, G., Zetler, G., Schlosser, Lucie: Structure-activity relationship of intracerebrally injected tremorigenic indole alkaloids. Neuropharmacology 12, 239–244 (1973)Google Scholar
  23. Tanz, R. D., Robbins, J. B., Kemple, K. L., Allen, P. A.: Pharmacology of aconitine-induced automaticity of cat papillary muscle. I. Effect of dose, tension, rate and endogenous catecholamines. J. Pharmacol. exp. Ther. 185, 427–437 (1973)Google Scholar
  24. Thompson, E. B., West, T. C.: Antagonism by propranolol of the cardiac chronotropic response to norepinephrine or to transmural electrical stimulation. J. Pharmacol. exp. Ther. 161, 232–237 (1968)Google Scholar
  25. Trendelenburg, U.: The action of histamine and 5-hydroxytryptamine on isolated mammalian atria. J. Pharmacol. exp. Ther. 130, 450–460 (1960)Google Scholar
  26. Trendelenburg, U.: The effect of sympathetic nerve stimulation on isolated atria of guinea pigs and rabbits pretreated with reserpine. J. Pharmacol. exp. Ther. 147, 313–318 (1965)Google Scholar
  27. Trendelenburg, U.: Classification of sympathomimetic amines. In: Handbook of experimental Pharmacology. H. Blaschko and E. Muscholl, Eds. Berlin-Heidelberg-New York: Springer 1972Google Scholar
  28. Trendelenburg, U., Crout, J. R.: The norepinephrine stores of isolated atria of guinea pigs pretreated with reserpine. J. Pharmacol. exp. Ther. 145, 151–161 (1964)Google Scholar
  29. Wagner, J.: Effect of phentolamine on isolated guinea-pig atria. Europ. J. Pharmacol. 9, 276–280 (1970)Google Scholar
  30. Zetler, G.: Einige pharmakologische Eigenschaften von 12 natürlichen und 11 partialsynthetisch abgewandelten Indol-Alkaloiden aus tropischen Apocynaceen des Substribus Tabernaemontaninae. Arzneimittel-Forsch. 14, 1277–1286 (1964)Google Scholar
  31. Zetler, G., Lenschow, E., Prenger-Berninghoff, W.: Die Wirkung von 11 Indol-Alkaloiden auf das Meerschweinchenherz in vivo und in vitro, verglichen mit 2 synthetischen Azepinoindolen, Chinidin und Quindonium. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. 260, 26–49 (1968)Google Scholar
  32. Zetler, G., Lessau, W.: Refractory period and strophanthin actions, as influenced by four indole alkaloids and two synthetic azepinoindoles. Pharmacology 8, 235–243 (1972)Google Scholar
  33. Zetler, G., Singbartl, G.: Inhibition of cardiac effects of noradrenaline by eleven indole alkaloids, two azepinoindoles, quinidine, quindonium, and propranolol. Pharmacology 4, 129–142 (1970)Google Scholar
  34. Zetler, G., Signbartl, G., Schlosser, Lucie: Cerebral pharmacokinetics of tremorproducing harmala and iboga alkaloids. Pharmacology 7, 237–248 (1972)Google Scholar

Copyright information

© Springer-Verlag 1974

Authors and Affiliations

  • G. Zetler
    • 1
  1. 1.Institut für Pharmakologie der Medizinischen Hochschule LübeckLübeckGermany

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