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

• Published in: British journal of pharmacology Vol. 85; no. 3; pp. 599 - 608
• Main Authors: Brown, R.A., Dixon, J., Farmer, J.B., Hall, Janet C., Humphries, R.G., Ince, F., O'Connor, S.E., Simpson, W.T., Smith, G.W.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.07.1985; Nature Publishing
• Subjects: Biological and medical sciences; Cardiovascular system; Medical sciences; Miscellaneous; Pharmacology. Drug treatments; Heart failure; Β2-Adrenergic receptor; Fissipedia; Carnivora; Vertebrata; Mammalia; Animal; Dopamine agonist; Dog; Biological activity; Dopaminergic receptor
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1985.tb10554.x

1 Dopexamine is an agonist at peripheral dopamine receptors and at β2‐adrenoceptors. 2 Dopexamine has approximately one‐third 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 × 10−8 mol kg−1 (i.a.). 3 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 × 10−6 M) and of neurogenic tachycardia in the cat (ID50 of 5.4 × 10−8 mol kg−1, i.v.), with a potency six and four times less respectively than that of dopamine. 4 By contrast, dopexamine is approximately 60 times more potent than dopamine as an agonist at the β2‐adrenoceptor of the guinea‐pig isolated tracheal chain, with an EC50 of 1.5 × 10−6 M. 5 Both dopexamine and dopamine are weak agonists at the guinea‐pig atrial β1‐adrenoceptor over the concentration range 10−7 to 10−4 M, but dopexamine has an intrinsic activity of only 0.16 relative to dopamine. 6 Dopexamine does not stimulate postjunctional α1 or α2‐adrenoceptors in the canine isolated saphenous vein, whereas dopamine is an agonist, approximately 120 times less potent than noradrenaline. 7 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. 8 The combination of agonist properties at peripheral dopamine receptors and at β2‐adrenoceptors, with little or no activity at α‐ and β1‐adrenoceptors gives dopexamine a novel pharmacological profile. This may confer advantages over dopamine in the treatment of acute heart failure.