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Pharmacological characteristics of liriodenine, isolated from Fissistigma glaucescens , a novel muscarinic receptor antagonist in guinea‐pigs
Author(s) -
Lin ChienHuang,
Chang GwoJyh,
Su MingJai,
Wu YangChang,
Teng CheMing,
Ko FengNien
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb16205.x
Subject(s) - muscarinic acetylcholine receptor , methoctramine , carbachol , neurokinin a , guinea pig , pirenzepine , trachealis muscle , antagonist , apamin , chemistry , endocrinology , tachykinin receptor , medicine , pharmacology , biology , receptor , substance p , neuropeptide , smooth muscle , charybdotoxin
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 μ m ) partially depressed the contractions induced by U‐46619, histamine, prostaglandin F 2a , 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 μ m ) did not affect U‐46619‐ or neurokinin A‐induced tracheal contraction in the presence of nifedipine (1 μ m ) or in Ca 2+ ‐free (containing 0.2 m m EGTA) medium. 7 Neither cyclic AMP nor cyclic GMP content of guinea‐pig trachealis was changed by liriodenine (30–300 μ 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 Ca 2+ channels at a high concentration (300 μ m ).