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[Dopexamine: a new dopaminergic agonist]

G Perrin, L Papazian, C Martin
Annales Françaises D'anesthèsie et de Rèanimation 1993, 12 (3): 308-20
7902685
Dopexamine hydrochloride is a new synthetic catecholamine for intravenous use in low cardiac output states with co-existing raised systemic or pulmonary vascular resistance. Dopamine has been commonly used since several years in these situations. The drawbacks of dopamine include a vasoconstrictive effect with high infusion rates, and a marked tendency for ventricular ectopy due to the potent beta-1 adrenergic stimulation. Dopexamine hydrochloride has interesting vasodilator properties, with marked intrinsic agonist activity at beta-2 adrenoreceptors and a lesser agonist activity at dopaminergic receptors (DA1 and DA2). Its mild inotropic activity arises primarily from baroreceptor reflex stimulation with a possible contribution from direct stimulation of myocardial beta 2-adrenoreceptors. Dopexamine hydrochloride is responsible for an inhibition of neuronal re-uptake of catecholamines (uptake-1), producing an indirect stimulation of cardiac beta 1-receptors. This catecholamine has no effect at alpha 1 and alpha 2-adrenoreceptors, and only very weak and clinically insignificant beta 1-adrenoreceptor agonist activity. Dopexamine hydrochloride improves cardiac performance by a marked vasodilation and a mild inotropic activity. The specific activity at dopaminergic receptors increases cerebral, myocardial, splanchnic and renal blood flows. These haemodynamic effects are associated with an increase in diuresis and natriuresis. These benefits are achieved without side effects such as an increased myocardial oxygen consumption, although induced tachycardia may be responsible for chest pain/anginae pain in patients with ischaemic heart disease. In clinical practice, dopexamine hydrochloride is easy to use; the short plasma half-life (6 minutes in healthy volunteers and 11 minutes in patients with low cardiac output) allows a rapid return to pretreatment status at discontinuation of the infusion. Preliminary studies have shown that dopexamine hydrochloride can produce beneficial effects in patients with acute heart failure or with compromised left ventricular function following cardiac surgery. The drug has also been assessed in patients with septic shock, most often in association with dopamine or norepinephrine. In these patients, dopexamine produces a dose-related increase in cardiac index, stroke volume, heart rate and a decrease in systemic vascular resistance. Its use in this indication must be cautious, particularly in patients with hypotension or decreased venous return. Comparative therapeutic trials are clearly required to establish the efficiency and tolerance of dopexamine hydrochloride in comparison with dopamine and dobutamine, before its place in therapy can fully be defined.

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