Ibopamine

Abstract

Ibopamine is an orally administered dopamine agonist which is rapidly converted to its active metabolite epinine by esterase hydrolysis. Ibopamine acts predominantly as a vasodilator and inhibitor of neuroendocrine activation in congestive heart failure, but also has mild positive inotropic effects at higher doses. The beneficial effects on cardiac and systemic haemodynamic parameters seen in short term studies have been maintained in predominantly noncomparative trials for up to 1 year, and improvements in New York Heart Association (NYHA) functional class and clinical symptoms have been observed in patients with congestive heart failure of varying severity. In double-blind studies conducted in small numbers of patients, the efficacy of ibopamine was comparable to that of digoxin, captopril, enalapril and hydrochlorothiazide. Ibopamine can successfully replace treatment with intravenous dopamine in patients with severe heart failure, and is effective and well tolerated when administered in combination with digoxin, diuretics and/or angiotensin converting enzyme (ACE) inhibitors. Ibopamine has shown no detrimental effects on renal function, few adverse effects on neurohormonal parameters and has demonstrated no significant proarrhythmic properties at therapeutic doses in patients with congestive heart failure. No adverse metabolic effects were observed during ibopamine therapy in patients with diabetes mellitus, nor did ibopamine have detrimental effects in patients with chronic obstructive pulmonary disease. While reliable evidence is required concerning effects on mortality before the role of ibopamine can be clearly defined, the drug appears to be a useful agent for combination with conventional therapies in treating patients with mild to severe congestive heart failure.

Dose-dependent separation of dopaminergic and adrenergic effects of epinine in healthy volunteers

“…The lack of any decreasing effect on heart rate or plasma noradrenaline levels that has been observed also in other studies in healthy volunteers for dopamine (Pernet et al 1984;Levinson et al 1985;Os et al 1987;Ensinger et al 1993) and epinine (Van Veldhuisen et al 1991;Girbes et al 1992;Brodde et al 1993) is compatible with the view that under normal physiologic conditions presynaptic DA-2 receptors do not play an important role in modulating noradrenaline release from sympathetic nerve endings (Lokhandwala and Barrett 1992); they may play a role only in situations of high sympathetic drive, for example in chronic heart failure (Packer 1992) where in fact ibopamine (respectively its active metabolite epinine) has been shown in many studies to reduce (the previously elevated) plasma noradrenaline levels (for references see Spencer et al 1993). Since in our study we have investigated healthy volunteers with normal sympathetic activity this might explain the lack of any decrease in heart rate and/or plasma noradrenaline levels following the dopamine or epinine infusion.…”

“…Since in these doses epinine acts only at DA-receptors (see above) these results provide direct evidence that ibopamine -in the above mentioned doses-exerts its effects only through activation of DA-2 (and possibly DA-1) receptors but does not affect ~-and fi-adrenergic receptors. Thus, the beneficial effects of ibopamine observed in treatment of patients with chronic heart failure (Henwood and Todd 1989;Taylor 1989;Spencer et al 1993;Kayanakis 1991) are not due to/3-or c~-adrenoceptor stimulation but are very likely due to activation of only DA-2 (and DA-1) receptors.…”

“…Based on these considerations two orally active dopaminergic drugs have been investigated in patients with chronic heart failure: levodopa (Rajfer et al 1987;Hasenfuss et al 1987) and ibopamine (for references see Henwood and Todd 1989;Taylor 1989;Spencer et al 1993). Ibopamine is the 3,4-diisobutyryl ester of Nmethyl-dopamine (epinine), and, after oral administration, is rapidly converted into epinine by plasma (and tissue) esterases.…”