Cardiovascular Effects of Plant Secondary Metabolites Norarmepavine, Coclaurine and Norcoclaurine

Abstract

Tbe cardiovascular etTeets of (±)-norannepavine, a benzylisoquinoline alkaloid of natural origin, have been detennined on anaesthetized rats in vivo, on spontaneously beating atria and on aortic smooth muscle. In aorta, the etTeets of (±)-coclaurine and (±)-norcoclaurine, benzylisoquinolines with a related structure, were a1so compared. (±)-Norarmepavine (10 mg/kg i.v.) decreased the mean arterial pressure and heart rate by 45% and 21 %, respectively. (±).Norannepavine (10-5_10-3 M) showed a negative chronotropic etTect on rat-iso· lated atria, decreasing the spontaneous frequency by about 54%. Aortic rings contracted with KCI 70 mM were relaxed in a concentration-dependent manner by (±). norannepavine, (±)-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 ealcium-dependent contraction eurves, denoting a calcium antagonist-like etTect; however, only a 10-fold increment of (±)-noreoclaurine concentration produced an equivalent etTect. Our results demonstrate the hypotensive and bradycardic properties of (±)-norannepavine. It is proposed that this alkaloid could somehow modulate calcium entry, its intracellular release or the calcium sensitivity of the cell eontractile-machinery, previously postulated for coclaurine. (±)Norcoclaurine etTects reported here are not in agreement with the proposal of (±)-norcoclaurine as a calcium channel activator or p.-adrenoceptor agonist.