Comparative effects of β-carbolines on platelet aggregation and lipid membranes

The effects of 14 β-carbolines on human platelet aggregability were comparatively studied,and the effects on lipid membranes were determined. several β-carbolines inhibited platelet aggregation induced by collagen,epinephrine,adenosine 5'-diphosphate,platelet-activating factor and thrombin. this activity was structure-dependent. of all the compounds examined,1-methyl-1,2,3,4-tetrahydro-β-carboline was the most potent. treatment with 15-177 μm 1 methyl-1,2,3,4-tetrahydro-β-carboline inhibited the aggregation responses to different stimulants by up to 50%. its potency was comparable to or greater than that of the antiplatelet reference,aspirin. the next most effective compound was 1-methyl-3,4-dihydro-β-carboline. the structure-antiplatelet activity relationship indicated that this activity is reduced by oxidation to 1-methyl-β-carboline,by demethylation to 1,2,3,4-tetrahydro-β-carboline and by 6 hydroxylation,7-hydroxylation and 3-carboxylation. active 1-methyl-1,2,3,4-tetrahydro-β-carboline fluidized biomimetic membranes at 25-250 μm which corresponded to the antiaggregatory concentrations,although relatively inactive 6-hydroxy-1-methyl-1,2,3,4-tetrahydro-β-carboline showed no significant effects on the membranes. β carbolines are considered to be effective antiplatelet agents that inhibit human platelet aggregation by interacting with lipid membranes to modify fluidity. © 2010 by institute of pharmacology polish academy of sciences.