Effects of harmala alkaloids on transmembrane potentials of guinea-pig papillary muscles.
1 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 degrees C and exposed to harmine or its analogue harmane, in which the methoxy group has been removed from the molecule. 2 Harmine 2 x 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 propranolol. Harmane 2 x 10(-5) M did not have any effect on normal action potentials and slow responses. 3 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. 4 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.
D000200:Action Potentials / Q000187:drug effects; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D004558:Electric Stimulation; D006168:Guinea Pigs; D006247:Harmine / Q000031:analogs & derivatives / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D013329:Structure-Activity Relationship; D013997:Time Factors
D000470:Alkaloids; D006247:Harmine; C005010:harman