CARDIOVASCULAR EFFECTS OF PLANT SECONDARY METABOLITES NORARMEPAVINE, COCLAURINE AND NORCOCLAURINE

The cardiovascular effects of (+/-)-norarmepavine, a benzylisoquinolin e alkaloid of natural origin, have been determined on anaesthetized ra ts in vivo, on spontaneously beating atria and on aortic smooth muscle . In aorta, the effects of (+/-)-coclaurine and (+/-)-norcoclaurine, b enzylisoquinolines with a related structure, were also compared. (+/-) -Norarmepavine (10 mg/kg i.v.) decreased the mean arterial pressure an d heart rate by 45% and 21%, respectively. (+/-)-Norarmepavine (10(-5) -10(-3) M) showed a negative chronotropic effect on rat-isolated atria , decreasing the spontaneous frequency by about 54%. Aortic rings cont racted with KCI 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 m ethylation of these compounds. The rank order of potency was: (+/-)-ve rapamil > (+/-)-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 equiv alent effect. Our results demonstrate the hypotensive and bradycardic properties of (+/-)-norarmepavine, It is proposed that this alkaloid c ould somehow modulate calcium entry, its intracellular release or the calcium sensitivity of the cell contractile-machinery, previously post ulated for coclaurine, (+/-)-Norcoclaurine effects reported here are n ot in agreement with the proposal of (+/-)-norcoclaurine as a calcium channel activator or beta(1)-adrenoceptor agonist, (C) 1998 John Wiley & Sons, Ltd.