Pyridazines. XVIII. 6-Aryl-3(2H)-pyridazinones inhibit calcium influx in stimulated platelets.
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.
Montero-Lastres
A
A
Laboratorio de Farmacología, Facultad de Farmacia, Universidad de Santiago de Compostela, Spain.
Fraiz
N
N
Laguna
R
R
Cano
E
E
Estevez
I
I
Raviña
E
E
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
D010975:Platelet Aggregation Inhibitors; D011724:Pyridazines; D015759:Ionomycin; D013917:Thrombin; D002118:Calcium