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 microM) partially depressed the contractions induced by U-46619, histamine, prostaglandin F2 alpha, 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 microM) did not affect U-46619- or neurokinin A-induced tracheal contraction in the presence of nifedipine (1 microM) or in Ca(2+)-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 microM). 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 microM).
Lin
C H
CH
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei.
Chang
G J
GJ
Su
M J
MJ
Wu
Y C
YC
Teng
C M
CM
Ko
F N
FN
D000818:Animals; D001060:Aporphines / Q000302:isolation & purification / Q000494:pharmacology*; D002217:Carbachol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D018727:Muscarinic Antagonists; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D010946:Plants, Medicinal / Q000737:chemistry*; D014132:Trachea / Q000187:drug effects / Q000378:metabolism
D001060:Aporphines; D018727:Muscarinic Antagonists; D002217:Carbachol; D000242:Cyclic AMP; C026980:liriodenine; D006152:Cyclic GMP