PHARMACOLOGICAL CHARACTERISTICS OF LIRIODENINE, ISOLATED FROM FISSISTIGMA-GLAUCESCENS, A NOVEL MUSCARINIC RECEPTOR ANTAGONIST IN GUINEA-PIGS

1 The pharmacological activities of liriodenine, isolated from Fissistigma glaucescens, were determined in isolated trachea, ileum and cardiac tissues of guinea-pigs. 2 Liriodenine was found to be a muscarinic receptor antagonist in guinea-pig trachea as revealed by its competitive antagonism of carbachol (pA(2) = 6.22 +/- 0.08)-induced smooth muscle contraction. It was slightly more potent than methoctramine (pA(2) = 5.92 +/- 0.05), but was less potent than atropine (pA(2) = 8.93 +/- 0.07), pirenzepine (pA(2) = 7.02 +/- 0.09) and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP, pA(2) = 8.72 +/- 0.07). 3 Liriodenine was also a muscarinic antagonist in guinea-pig ileum (pA(2) = 6.36 +/- 0.10) with a pA(2) value that closely resembled that obtained in the trachea. 4 Liriodenine was 10 fold less potent in atrial preparations (left atria, pA(2) = 5.24 +/- 0.04; right atria, pA(2) = 5.35 +/- 0.09 and 5.28 +/- 0.07 for inotropic and chronotropic effects, respectively) than in smooth muscle preparations. 5 High concentration of liriodenine (300 mu M) partially depressed the contractions induced by U-46619, histamine, prostaglandin F-2 alpha, neurokinin A, leukotriene C-4 and high K-+ in the guinea-pig trachea. The inhibitions were characterized by a rightward shift in the concentration-response curves with suppression of their maximal contraction. 6 High concentration of liriodenine (300 mu M) did not affect U-46619- or neurokinin A-induced tracheal contraction in the presence of nifedipine (1 mu M) or in Ca2+-free (containing 0.2 mM EGTA) medium. 7 Neither cyclic AMP nor cyclic GMP content of guinea-pig trachealis was changed by liriodenine (30-300 mu M). 8 It is concluded that liriodenine is a selective muscarinic receptor antagonist in isolated trachea, ileum and cardiac tissues of guinea-pigs. It is more potent in smooth muscle than in cardiac preparations. It also acts as a blocker of voltage-dependent Ca2+ channels at a high concentration (300 mu M).