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• W2002094125 abstract "Clonidine (2-[(2,6-dichlorophenyl)amino]-2-imidazoline), an imidazoline alpha(2)-adrenoceptor agonist, is known to exert complex effects on human platelet aggregation distinct from those of the catecholamines, which are non-imidazoline alpha-adrenoceptor agonists. This study has investigated the aggregatory/anti-aggregatory effects of various imidazolines on human platelets. Blood samples were taken from normal volunteers and platelet aggregation was assessed by a turbidimetric method using a Chronolog aggregometer. Noradrenaline (2 microM) and adenosine diphosphate (1 microM) were used as aggregating agents. The results showed that, with the exception of moxonidine, all of the imidazoline agents used (with or without alpha(2)-adrenoceptor activity) were able to inhibit noradrenaline-induced platelet aggregation. Compared with the non-imidazoline alpha(2)-adrenergic antagonist, yohimbine, the rank order of potency was: efaroxan (IC50 = 3.07 x 10(-8) M) > idazoxan (IC50 = 1.74 x 10(-7) M) > tolazoline (IC50 = 3.90 x 10(-7) M) > clonidine (IC50 = 1.49 x 10(-6) M) congruent with antazoline (IC50 = 1.77 x 10(-6) M) > yohimbine (IC50 = 3.19 x 10(-6) M) > rilmenidine (IC50 = 1.27 x 10(-5) M) > moxonidine (IC50 > 10(-4) M). Clonidine-displacing substance (CDS), a putative endogenous ligand at imidazoline receptors, was found to inhibit noradrenaline-induced platelet aggregation. Harmane, norharmane and agmatine, putative candidates for the active principle of CDS, had no effect on noradrenaline-induced platelet aggregation. In contrast to noradrenaline-induced aggregation, ADP-induced platelet aggregation was neither potentiated nor inhibited by the imidazoline agents, with the exceptions of clonidine and moxonidine. In conclusion, most imidazoline agents effectively inhibit noradrenaline-induced human platelet aggregation. The lack of effect of moxonidine and the proposed endogenous ligands suggested this effect was mediated by an 'atypical' non-adrenoceptor imidazoline-binding site. The results indicated an anti-aggregatory role of imidazoline compounds on noradrenaline-induced human platelet aggregation. In addition, CDS might be an endogenous modulator that prevented platelet hyper-reactivity to catecholamine stimulation." @default.
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• W2002094125 date "2004-02-01" @default.
• W2002094125 modified "2023-10-06" @default.
• W2002094125 title "The effects of imidazoline agents on the aggregation of human platelets" @default.
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• W2002094125 doi "https://doi.org/10.1211/0022357022593" @default.
• W2002094125 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15005880" @default.
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