Ibopamine

Abstract

In comparison to other endogenous catecholamines, dopamine (DA) has unique cardiovascular properties. Goldberg et al. (30,34,54) perceived the therapeutic potential of intravenous DA infusion in refractory congestive heart failure as early as 1963-1964, when the mechanisms of its pharmacological effects were not yet well understood. Over several years of laboratory and clinical studies, the complex of adrenergic and specific dopaminergic effects determining the clinical effects of DA have been unraveled (31,33,35,45,46). Experience has also accumulated that allows for qualitative and quantitative modulation of the activity of DA by the adjustment of infusion rates (31,32). At the lowest rates, two subtypes of dopaminergic receptors are activated: DA, receptors, which mediate vasodilatation in the renal, mesenteric, cerebral, and coronary vascular beds; and DA, receptors, whose activation results in the inhibition of the sympathetic nervous system by decreasing release of norepinephrine from postganglionic sympathic nerve endings. At higher infusion rates of DA, beta, receptors are activated, resulting in cardiac stimulation. At still higher doses, alpha, and alpha, receptors are activated and vasoconstriction occurs. In congestive heart failure, DA is infused at rates that will activate DA and beta receptors, while in the treatment of shock, higher infusion rates of DA are used to stimulate alpha receptors in order to increase perfusion pressure. Although DA is now established as the drug of choice for the therapy of shock (28), its usefulness in the treatment of heart failure remains limited because of its ineffectiveness by oral administration. Goldberg (30,31) emphasized the therapeutic potential of an orally active form of DA for the chronic treatment of congestive heart failure.In recent years the development of new, orally active analogs of DA has been attempted by several research groups. Our laboratory's approach focused on the cardiovascular properties of the new compounds and led to the discovery of ibopamine. MEDICINAL CHEMISTRYThe chemical name of ibopamine (INN, USAN) is 4-[2-(methylamino ethyl)]-o-phenylene diisobutyrate, or N-methyl-3,4-O-diisobutyryldopamine (Fig. 1). Its laboratory code was SB 7505; ibopamine is also known by the trade names Inopamil and Scandine. 173

Peripheral hemodynamic effects of ibopamine in patients with congestive heart failure. A placebo-controlled, double-blind study

“…It is the di-isobutyric ester of N-methyl-dopamine, which after absorption is hydrolyzed to epinine [1]. It is the di-isobutyric ester of N-methyl-dopamine, which after absorption is hydrolyzed to epinine [1].…”

Ibopamine versus hydrochlorothiazide/amiloride in patients with mild congestive heart failure

“…In our trial we compared the relative clinical benefit of using either ibopamine, a dopamine-related, positive inotropic agent with vasodilating activities [6], as a single agent, or diuretic therapy in patients with mild CHF (NYHA Class III.…”

Six-Month Treatment of Congestive Heart Failure with Ibopamine: A Double-Blind Randomized, Placebo-Controlled Multicenter Trial

“…This com pound produces a selective stimulation of peripheral (vascular) dopamine receptors [8] which results in a sig-nificant reduction in systemic and renal vascular resis tance [9]. The decrease in systemic vascular resistance is accompanied by an increase in cardiac output, usually without alteration of heart rate or blood pressure.…”