Dopexamine: a novel agonist at peripheral dopamine receptors and β2‐adrenoceptors

Abstract

Dopexamine is an agonist at peripheral dopamine receptors and at .beta.2-adrenoceptors. Dopexamine has approximately 1/3 the potency of dopamine in stimulating the vascular DA1-receptor in the dog, resulting in a fall in renal vascular resistance of 20% at 2.3 .times. 10-8 mol kg-1 (i.a. [intraarterial]). Prejunctional DA2-receptors are also stimulated by dopexamine, resulting in a reduction of neurogenic vasoconstriction in the rabbit isolated ear artery (IC50 of 1.15 .times. 10-6 M) and of neurogenic tachycardia in the cat (ID50 of 5.4 .times. 10-8 mol kg-1, i.v.), with a potency 6 and 4 times less, respectively, than that of dopamine. By contrast, dopexamine is .apprx. 60 times more potent than dopamine as an agonist at the .beta.2-adrenoceptor of the guinea pig isolated tracheal chain, with an EC50 of 1.5 .times. 10-6 M. Both dopexamine and dopamine are weak agonists at the guinea pig atrial .beta.1-adrenoceptor over the concentration range 10-7 to 10-4 M, but dopexamine has an intrinsic activity of only 0.16 relative to dopamine. Dopexamine does not stimulate postjunctional .alpha.1- or .alpha.2-adrenoceptors in the canine isolated saphenous vein, whereas dopamine is an agonist, .apprx. 120 times less potent than noradrenaline [norepinephrine]. Unlike dopamine and salbutamol, dopexamine does not cause arrhythmias in the guinea pig isolated perfused heart at doses of up to 10-5 mol, which is a thousand times the minimum cardiostimulant dose. The combination of agonist properties at peripheral dopamine receptors and at .beta.2-adrenoceptors, with little or no activity at .alpha.- and .beta.1-adrenoceptors gives dopexamine a novel pharmacological profile. This may confer advantages over dopamine in the treatment of acute heart failure.