The cardiovascular effects of (AE)-norarmepavine, a benzylisoquinoline alkaloid of natural origin, have been determined on anaesthetized rats in vivo, on spontaneously beating atria and on aortic smooth muscle. In aorta, the effects of (AE)-coclaurine and (AE)-norcoclaurine, benzylisoquinolines with a related structure, were also compared.
(AE)-Norarmepavine (10 mg/kg i.v.) decreased the mean arterial pressure and heart rate by 45% and 21%, respectively. (AE)-Norarmepavine (10 ร5 -10 ร3 M) showed a negative chronotropic effect on rat-isolated atria, decreasing the spontaneous frequency by about 54%.
Aortic rings contracted with
KCl 70 mM were relaxed in a concentration-dependent manner by (AE)norarmepavine, (AE)-coclaurine and (AE)-norcoclaurine (10 ร6 -10 ร3 M). The two earlier alkaloids exhibited an efficacy similar to verapamil, relaxing the aortic rings by 100%. (AE)-Norcoclaurine exhibited a lower efficacy. These results point to the importance of methylation of these compounds. The rank order of potency was: (AE)-verapamil b (AE)-norarmepavine b (AE)-norcoclaurine b (AE)-coclaurine.
The alkaloids shifted to the right the calcium-dependent contraction curves, denoting a calcium antagonist-like effect; however, only a 10-fold increment of (AE)-norcoclaurine concentration produced an equivalent effect. Our results demonstrate the hypotensive and bradycardic properties of (AE)-norarmepavine. It is proposed that this alkaloid could somehow modulate calcium entry, its intracellular release or the calcium sensitivity of the cell contractile-machinery, previously postulated for coclaurine. (AE)-Norcoclaurine effects reported here are not in agreement with the proposal of (AE)-norcoclaurine as a calcium channel activator or b 1 -adrenoceptor agonist.