Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D02027 (Tranilast)
 205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanism proposed to explain the antiasthmatic antiallergic action of Tranilast is the inhibition of chemical mediator release from mast cells and leukocytes as well as the antagonism of smooth muscle contracting activity of leukotrienes. It has been shown that this drug inhibits platelet aggregation induced "in vitro" by different stimuli. We investigated the effect of Tranilast on the release of thromboxane from guinea pig isolated lungs stimulated by the calcium ionophore A 23187 and the contraction of smooth muscle induced by this eicosanoid. Tranilast did not inhibit the release of arachidonic acid metabolites from the lungs but it prevented the contraction of the rat aorta induced by thromboxane released from lungs. Moreover, the drug antagonized the contraction of rat and rabbit isolated aortas stimulated by the thromboxane/endoperoxide mimetic U 46619. These effects might be mediated by a blockade of calcium uptake, since the drug was able to induce the relaxation of rabbit aortas previously contracted by potassium. Calcium ions are involved in the activation of mast cells, leukocytes, platelets and smooth muscle; therefore, the inhibition of calcium uptake might mediate the pharmacological properties of Tranilast.
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PMID:New approach to the mechanism of antiasthmatic action of Tranilast. 169 24

The anti-allergic activity and mechanism of cinnarizine was investigated in guinea pigs. Nifedipine, a calcium antagonist, and tranilast, a potent, orally active anti-allergic agent, were used as comparative drugs. Cinnarizine protected against fatal systemic anaphylactic shock in guinea pigs passively sensitized with IgE antibody. Cinnarizine reduced many of the features of severe respiratory disorders. Nifedipine and tranilast showed similar effects. Cinnarizine and nifedipine inhibited the contractile response to antigen of sensitized tracheal smooth muscle when the challenge was carried out at low antigen concentrations. Tranilast showed a tendency to inhibit the antigen-induced contraction of tracheal smooth muscle. Cinnarizine and nifedipine inhibited Ca-induced contraction in potassium-depolarized tracheal smooth muscle, tranilast had no effect. Cinnarizine showed antagonistic action to the contraction by histamine or leukotriene D4 (LTD4) of tracheal muscle. Nifedipine showed similar antagonistic action, although its potency is lower than cinnarizine. Tranilast showed slight antagonistic action to LTD4. Antigen-induced release of histamine and slow reacting substance of anaphylaxis (SRS-A) from sensitized lung tissues was inhibited by nifedipine and tranilast but not by cinnarizine. The release of histamine and SRS-A from lung tissues by calcium ionophore A23187 was inhibited by nifedipine and tranilast but not by cinnarizine. These results suggest that the anti-allergic action of cinnarizine is mainly due to the antagonistic action to allergic mediators and not by interfering with the release of mediators. Cinnarizine's mechanism seems to be related to its antagonistic action to Ca in smooth muscle, but not to the transport of Ca in releasing the anaphylactic chemical mediators in mast cells and other target cells.
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PMID:Effect of cinnarizine on IgE antibody-mediated experimental allergic reactions in guinea pigs. 243 61

N-(3',4'-dimethoxycinnamoyl) anthranilic acid (tranilast), an effective anti-allergic drug, has successfully prevented restenosis in patients who have undergone percutaneous transluminal coronary angioplasty. To elucidate the mechanism of tranilast, we investigated its antagonistic effect to angiotensin II, which plays a pivotal role in the proliferation of vascular smooth muscle cells, using angiotensin II-induced contractions in human gastroepiploic artery and rabbit aorta. The possible antagonistic effects of other anti-allergic agents such as 4-( p-chlorobenzyl)-2-(hexahydro-1-methyl-1H-azepin-4-yl)-1(2H)-phthal azinone hydrochloride (azelastine), 9-methyl-3-( 1H-tetrazol-5-yl)-4H-pyrido[1,2-a]pyramidin-4-one potassium salt (pemirolast) and disodium cromoglycate were also compared. Tranilast dose-dependently inhibited the angiotensin II-induced contractions in human and rabbit arteries (IC50 = 3.6x10(-5) M and pD'2 = 3.69, respectively). Pemirolast showed a weak antagonistic effect to angiotensin II, but the effective concentration cannot be administered in clinical dosage. Tranilast and pemirolast had no effect on the concentration-contractile response curves for KCI and norepinephrine. Azelastine inhibited angiotensin II-, KCl- and norepinephrine-induced contractions non-specifically, while disodium cromoglycate did not affect these contractile responses. Tranilast but not azelastine showed synergistic action with 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimi dazole-7-carboxylic acid (CV- 11974) in antagonizing angiotensin II-induced contraction and the inhibitory pattern was similar to that of the non-peptide angiotensin II AT1 receptor antagonist CV-11974. These findings indicate that only tranilast possesses the unique ability to antagonize angiotensin II in clinical dosage, which may contribute at least in part to prevention of restenosis after percutaneous transluminal coronary angioplasty.
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PMID:Tranilast, an anti-allergic drug, possesses antagonistic potency to angiotensin II. 986 9