Pharmacological characteristics of liriodenine, isolated from Fissistigma glaucescens, a novel muscarinic receptor antagonist in guinea‐pigs

The pharmacological activities of liriodenine, isolated from Fissistigma glaucescens, were determined in isolated trachea, ileum and cardiac tissues of guinea‐pigs. 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). 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. 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. High concentration of liriodenine (300 μm) partially depressed the contractions induced by U‐46619, histamine, prostaglandin F_2a, 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. 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. 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). 1994 British Pharmacological Society