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Mivazerol, a novel compound with high specificity for α2 adrenergic receptors: Binding studies on different human and rat membrane preparations

1994; Elsevier BV; Volume: 24; Issue: 3 Linguagem: Inglês

10.1016/0197-0186(94)90079-5

1872-9754

Michel Noyer, Françoise de Laveleye, Georges Vauquelin, J.G. Gobert, Ernst Wülfert,

Pharmacological Effects and Assays

Mivazerol, 3-[1(H-imidazol-4-yl)methyl]-2-hydroxybenzamide hydrochloride, a new potential anti-ischemic drug designed by UCB S.A. Pharma Sector, has been studied in binding experiments on adrenergic, dopaminergic, serotoninergic, muscarinic and idazoxan binding sites. Our results indicate that this compound displays high affinity and marked specificity for α2 adrenoceptors. Mivazerol displaced the binding of the α2 adrenoceptor antagonist [3H]RX 821002 to the α2A adrenoceptors in human frontal cortex membranes with an apparent Ki value of 37 nM. The competition curve was shallow (nH = 0.55), suggesting that this compound acts as an α2 adrenergic agonist. Mivazerol was also a potent competitor for [3H]RX 821002 binding to human platelet membranes (containing α2A adrenoceptors) and rat kidney membranes (75 % of the α2 adrenoceptors of the α2B subtype), indicating that this compound is not α2 adrenoceptor subtype selective. Equilibrium dissociation constants for α1 adrenoceptors (displacement of [3H]prazosin) and 5-HT1A receptors (displacement of [3H]rauwolscine) were respectively about 120 times (Ki = 4.4 μM) and 14 times (Ki = 530 nM) higher than that for the α2 adrenoceptors. Equilibrium dissociation constants were approximately 1000 times higher for all other receptors tested in this study; namely β1 and β2 adrenoceptors, D1- and D2-dopamine receptors, M1-, M2- and M3-muscarinic receptors, 5-HT2 receptors and non-adrenergic idazoxan bindings sites.