Dicentrine, a natural vascular alpha 1-adrenoceptor antagonist, isolated from Lindera megaphylla.

1. The pharmacological activity of dicentrine, isolated from Lindera megaphylla, was determined 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 microM) in rat thoracic aorta was suppressed by dicentrine (3-10 microM) and prazosin (3 microM). 4. A high concentration of dicentrine (30 microM) did not affect the aortic contraction induced by the thromboxane receptor agonist U-46619 (1 microM), angiotensin II (1 microM), high potassium (60 mM) or carbachol (3 microM). 5. Contraction of guinea-pig trachea caused by histamine or carbachol was slightly inhibited by dicentrine (30 microM), while beta-adrenoceptor relaxation to isoprenaline in trachea was not affected. 6. Aggregation in human platelet-rich plasma induced by adrenaline (10 microM) was blocked by yohimbine (5 microM). A high concentration of dicentrine (greater than 30 microM) caused slight inhibition of aggregation, the release reaction and thromboxane formation. Complete blockade was obtained with 150 microM dicentrine. 7. It is concluded that dicentrine is a potent, selective alpha 1-adrenoceptor antagonist in vascular smooth muscle.