EFFECTS OF HARMALA ALKALOIDS ON TRANSMEMBRANE POTENTIALS OF GUINEA‐PIG PAPILLARY MUSCLES

Abstract

The significance of the presence of a methoxy group in the 7 position of the indole nucleus of harmala alkaloids in terms of their effects on the action potential of cardiac muscle was analysed. Guinea‐pig papillary muscles were superfused with Tyrode solution at 30°C and exposed to harmine or its analogue harmane, in which the methoxy group has been removed from the molecule. Harmine 2 × 10−5 m enhanced the amplitude of the action potential (AAP) of normal fibres and of slow responses elicited by noradrenaline in fibres depolarized by 21.6 mm K+‐Tyrode. The effect of harmine on AAP occurred in the absence of any change in membrane resting potential or maximum velocity of the upstroke and it was abolished by propranol. Harmane 2 × 10−5 m did not have any effect on normal action potentials and slow responses. Higher concentrations of the two analogues depressed both AAP and the maximum velocity of the upstroke of the action potential, without affecting the duration of the action potential. It is concluded that: (a) removal of the methoxy group from harmine (1) abolishes the catechol‐mediated stimulatory effect of a low concentration of the drug on the slow component of the upstroke of the action potential, and (2) does not modify the depressant effect of a high concentration of the drug. (b) The two analogues, harmine and harmane, do not affect the duration of the action potential of ventricular muscle. 1982 British Pharmacological Society