Abstract

The cardiovascular effects of (±)-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 (±)-coclaurine and (±)-norcoclaurine, benzylisoquinolines with a related structure, were also compared. (±)-Norarmepavine (10 mg/kg i.v.) decreased the mean arterial pressure and heart rate by 45% and 21%, respectively. (±)-Norarmepavine (10 -5-10 -3 M) showed a negative chronotropic effect on rat-isolated atris, decreasing the spontaneous frequency by about 54%. Aortic rings contracted with KCl 70 mM were relaxed in a concentration-dependent manner by (±-)norarmepavine, (±)-coclaurine and (±)-norcoclaurine (10 -6-10 -3 M). The two earlier alkaloids exhibited an efficacy similar to verapamil, relaxing the aortic rings by 100%. (±)-Norcoclaurine exhibited a lower efficacy. These results point to the importance of methylation of these compounds. The rank order of potency was: (±)-verapamil > (±)-norarmepavine > (±)-norcoclaurine > (±)-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 (±)-norcoclaurine concentration produced an equivalent effect. Our results demonstrate the hypotensive and bradycardic properties of (±)-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. (±)-Norcoclaurine effects reported here are not in agreement with the proposal of (±)-norcoclaurine as a calcium channel activator or ? 1-adrenoceptor agonist.