PHARMACOLOGICAL CHARACTERISTICS OF LIRIODENINE, ISOLATED FROM FISSISTIGMA-GLAUCESCENS, A NOVEL MUSCARINIC RECEPTOR ANTAGONIST IN GUINEA-PIGS

被引:20
作者
LIN, CH
CHANG, GJ
SU, MJ
WU, YC
TENG, CM
KO, FN
机构
[1] NATL TAIWAN UNIV,COLL MED,INST PHARMACOL,SECT 1,TAIPEI 10018,TAIWAN
[2] KAOHSIUNG MED COLL,SCH PHARM,KAOHSIUNG,TAIWAN
关键词
MUSCARINIC RECEPTOR ANTAGONIST; CA2+ CHANNEL BLOCKER; GUINEA-PIG TRACHEA; LIRIODENINE; FISSISTIGMA GLAUCESCENS;
D O I
10.1111/j.1476-5381.1994.tb16205.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 mu M) partially depressed the contractions induced by U-46619, histamine, prostaglandin F-2 alpha, 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 mu M) did not affect U-46619- or neurokinin A-induced tracheal contraction in the presence of nifedipine (1 mu M) 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 mu 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 Ca2+ channels at a high concentration (300 mu M).
引用
收藏
页码:275 / 281
页数:7
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