title: Comparative effects of β-carbolines on platelet aggregation and lipid membranes.
abstract: 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.
authors.affiliation: Department of Dental Basic Education, Asahi University School of Dentistry, 1851-1 Hozumi, Mizuho, Gifu 501-0296, Japan. hiro@dent.asahi-u.sc.jp
authors.forename: Hironori
authors.initials: H
authors.lastname: Tsuchiya
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ohmoto
mesh_terms: D000328:Adult; D002243:Carbolines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D002243:Carbolines; D008051:Lipid Bilayers; D010975:Platelet Aggregation Inhibitors