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

Chien‐Huang ‐H Lin, Gwo‐Jyh ‐J Chang, Ming‐Jai ‐J Su, Yang‐Chang ‐C Wu, Che‐Ming ‐M Teng, Feng‐Nien ‐N Ko*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

34 Scopus citations

Abstract

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 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. 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

Original languageEnglish
Pages (from-to)275-281
Number of pages7
JournalBritish Journal of Pharmacology
Volume113
Issue number1
DOIs
StatePublished - 09 1994
Externally publishedYes

Keywords

  • Ca channel blocker
  • Fissistigma glaucescens
  • Muscarinic receptor antagonist
  • guinea‐pig trachea
  • liriodenine

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