title: Pyridazines. XVIII. 6-Aryl-3(2H)-pyridazinones inhibit calcium influx in stimulated platelets.
abstract: 6-Phenyl-5-hydroxymethyl-4,5-dihydro-3(2H)-pyridazinone (1) and 6-thienyl-5-hydroxymethyl-4,5-dihydro-3(2H)-pyridazinone (2) inhibit platelet aggregation induced by thrombin (IC50 = 0.25 and 0.26 mM, respectively) or by the calcium ionophore ionomycin (IC50 = 0.42 and 0.43 mM, respectively). Pyridazinones 1 and 2 also show concentration-dependent attenuation of the increases in platelet cytosolic free calcium concentration induced by thrombin and ionomycin, suggesting that their antiaggregatory activity may be due to their capacity to inhibit the passage of calcium through the cytoplasmic membrane. This effect may be implicated in other pharmacological activities of 6-aryl-5-substituted-pyridazinones.
authors.affiliation: Laboratorio de Farmacología, Facultad de Farmacia, Universidad de Santiago de Compostela, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Montero-Lastres
authors.forename: N
authors.initials: N
authors.lastname: Fraiz
authors.forename: R
authors.initials: R
authors.lastname: Laguna
authors.forename: E
authors.initials: E
authors.lastname: Cano
authors.forename: I
authors.initials: I
authors.lastname: Estevez
authors.forename: E
authors.initials: E
authors.lastname: Raviña
mesh_terms: D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D066298:In Vitro Techniques; D015759:Ionomycin / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology
chemical_list: D010975:Platelet Aggregation Inhibitors; D011724:Pyridazines; D015759:Ionomycin; D013917:Thrombin; D002118:Calcium