Effect of 781094, a new selective alpha-adrenoceptor antagonist, on the aggregatory responses of human blood platelets and on binding of [3H]-dihydroergocryptine to these cells.
781094 (2-(2(1, 4-benzodioxanyl))-2-imidazoline hydrochloride) is a potent competitive inhibitor of the aggregatory responses of human platelets induced by adrenaline (pA2 = 7.3) and UK-14304. 781094 is a more potent inhibitor of the pro-aggregatory response to clonidine than of that to methoxamine. The alpha 2/alpha 1-adrenoceptor selectivity ratio is 11.4. 781094 is a potent inhibitor of the binding of [3H]-dihydroergocryptine to platelet lysates. 781094 has no effect on the aggregatory responses of human platelets induced by adenosine-5'-pyrophosphate (ADP), 5-hydroxytryptamine, thrombin, U-46619, or arginine-vasopressin provided that the platelet-rich plasma does not exhibit enhanced responsiveness. In some instances high concentrations of 781094 potentiate the aggregatory response to collagen. In platelet-rich plasma which exhibits enhanced responsiveness, 781094 causes partial inhibition of the aggregatory responses to 5-hydroxytryptamine, ADP and vasopressin at concentrations similar to those required to inhibit the response to adrenaline. 781094 acts as a specific antagonist for the responses mediated by human platelet alpha-adrenoceptors and exhibits moderate selectivity for the alpha 2-adrenoceptors on this cell.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D001792:Blood Platelets / Q000378:metabolism*; D000068438:Brimonidine Tartrate; D003000:Clonidine / Q000494:pharmacology; D004088:Dihydroergotoxine / Q000378:metabolism*; D004147:Dioxins / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D019329:Idazoxan; D008729:Methoxamine / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D011810:Quinoxalines / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D014316:Tritium
D000317:Adrenergic alpha-Antagonists; D004147:Dioxins; D011810:Quinoxalines; D014316:Tritium; D004088:Dihydroergotoxine; D012701:Serotonin; D000068438:Brimonidine Tartrate; D008729:Methoxamine; D003000:Clonidine; D019329:Idazoxan; D004837:Epinephrine