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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
L-652,469--a dual receptor antagonist of platelet activating factor and dihydropyridines from Tussilago farfara L.
L-652,469, 14-acetoxy-7 beta-(3'-ethylcrotonoyloxy)-notonipetranone, isolated from the methylenechloride extracts of the buds of Tussilago farfara L, was found to inhibit both platelet activating factor (PAF) and Ca2+ entry blocker binding to membrane vesicles. It inhibits the [3H]PAF specific binding to rabbit platelet membranes with equilibrium inhibition constants (Ki) of 3.2 and 4.0 microM in the presence of 150 mM NaCl and 10 mM MgCl2 respectively. It is a competitive PAF receptor antagonist with an equilibrium dissociation constant (KB) of 5.16 microM. It also competitively inhibits the specific binding of Ca2+ channel blockers (e.g. [3H]nitrendipine; Ki = 1.2 microM) in cardiac sarcolemmal vesicles. At 10(-5) M, L-652,469 causes a 60% relaxation of Ca2+-induced contraction of rat thoracic aorta strips. Due to its dual antagonistic activities, L-652,469 potently inhibits the gel-filtered rabbit platelet aggregation with a pA2 of 5.79. It was also found to be orally active with a beneficial effect to inhibit the PAF-induced rat foot edema and the first phase of carrageenan-induced rat hindpaw edema.[1]
