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

  • Gerhard Zetler
  • Published 1974 in Naunyn-Schmiedeberg's Archives of Pharmacology

Abstract

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

DOI: 10.1007/BF00501143

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@article{Zetler1974IndirectCE, title={Indirect cardiac effects of indole, simple indole derivatives, and harmine}, author={Gerhard Zetler}, journal={Naunyn-Schmiedeberg's Archives of Pharmacology}, year={1974}, volume={283}, pages={165-179} }