DICENTRINE, A NATURAL VASCULAR ALPHA-1-ADRENOCEPTOR ANTAGONIST, ISOLATED FROM LINDERA-MEGAPHYLLA

1 The pharmacological activity of dicentrine, isolated from Lindera megaphylla, was determind in rat isolated thoracic aorta, guinea-pig isolated trachea and human platelet-rich plasma. 2 Dicentrine was found to be a potent alpha-1-adrenoceptor blocking agent in rat thoracic aorta as revealed by its competitive antagonism of noradrenaline- (pA2 = 8.19 +/- 0.09) or phenylephrine (pA2 = 9.01 +/- 0.10)-induced vasoconstriction. These effects still persisted in denuded aorta. It was less potent than prazosin (pA2 = 10.60 +/- 0.10), but was more potent than phentolamine (pA2 = 7.53 +/- 0.10) or yohimbine (pA2 = 6.20 +/- 0.05). 3 Inositol monophosphate formation induced by noradrenaline (3-mu-M) in rat thoracic aorta was suppressed by dicentrine (3-10-mu-M) and prazosin (3-mu-M). 4 A high concentration of dicentrine (30-mu-M) did not affect the aortic contraction induced by the thromboxane receptor agonist U-46619 (1-mu-M), angiotensin II (1-mu-M), high potassium (60 mM) or carbachol (3-mu-M). 5 Contraction of guinea-pig trachea caused by histamine or carbachol was slightly inhibited by dicentrine (30-mu-M), while beta-adrenoceptor relaxation to isoprenaline in trachea was not affected. 6 Aggregation in human platelet-rich plasma induced by adrenaline (10-mu-M) was blocked by yohimbine (5-mu-M). A high concentration of dicentrine (> 30-mu-M) caused slight inhibition of aggregation, the release reaction and thromboxane formation. Complete blockade was obtained with 150-mu-M dicentrine. 7 It is concluded that dicentrine is a potent, selective alpha-1-adrenoceptor antagonist in vascular smooth muscle.