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 (pA2 = 6.22 ± 0.08)‐induced smooth muscle contraction. It was slightly more potent than methoctramine (pA2 = 5.92 ± 0.05), but was less potent than atropine (pA2 = 8.93 ± 0.07), pirenzepine (pA2 = 7.02 ± 0.09) and 4‐diphenylacetoxy‐N‐methylpiperidine (4‐DAMP, pA2 = 8.72 ± 0.07). 3 Liriodenine was also a muscarinic antagonist in guinea‐pig ileum (pA2 = 6.36 ± 0.10) with a pA2 value that closely resembled that obtained in the trachea. 4 Liriodenine was 10 fold less potent in atrial preparations (left atria, pA2 = 5.24 ± 0.04; right atria, pA2 = 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 μm) partially depressed the contractions induced by U‐46619, histamine, prostaglandin F2a, neurokinin A, leukotriene C4 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 μm) did not affect U‐46619‐ or neurokinin A‐induced tracheal contraction in the presence of nifedipine (1 μm) 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 μm). 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 μm).