The effects of moxonidine, a novel imidazoline, on plasma norepinephrine in patients with congestive heart failure

Abstract

The increased sympathetic activation in CHF can be reduced by moxonidine through CNS inhibition.

The effect of β-adrenergic receptor antagonism in cardiac sympathetic neuronal remodeling in patients with heart failure

“…Such a reduction in plasma norepinephrine levels does not necessarily benefit the treatment of patients with heart failure. For example, the use of moxonidine decreased plasma norepinephrine levels in one study [32], but increased the incidence of hospital admissions and death compared to controls in other studies [33,34]. We propose that the benefit of drugs such as carvedilol is not related to the inhibition of adrenergic stimuli (central action); rather it reflects improved norepinephrine reuptake (buptake-IQ) by cardiac sympathetic neuronal terminals (peripheral action), as demonstrated in this study.…”

Antiadrenergic Therapy of Chronic Heart Failure

“…5 In phase II this compound was powerfully sympatholytic, and the degree of systemic norepinephrine reduction was directly associated with an increase in serious adverse events despite evidence for reverse remodeling, the signature of favorable antiadrenergic effects on the failing heart. 6 Because sympatholysis is the only known important pharmacological property of moxonidine, these data seriously challenged the uniform dogma that antiadrenergic therapy is beneficial. That sympatholysis is a harmful pharmacological property in a therapeutic agent used to treat CHF is further supported by data from the ␤-Blocker Evaluation of Survival (BEST) Trial, in which the unique ␤-blocker/sympatholytic agent bucindolol increased mortality in 14% of the treated population through a pronounced sympatholytic effect that was not observed in placebo-treated patients.…”

Renal Denervation for the Treatment of Cardiovascular High Risk-Hypertension or Beyond?

“…97 The rationale here is supported by the well-proven effect of neuroendocrine antagonists, such as angiotensin-converting enzyme inhibitors, β-blockers, and aldosterone antagonists to improve outcome in heart failure with reduced ejection fraction. 98 However, it has to be kept in mind that moxonodine, an antihypertensive agent, reducing central sympathetic nerve activity 99 and circulating norepinephrine concentrations, 100 was associated with increased morbidity and mortality. 101,102 In the future, adequately powered outcome trials are urgently needed to provide data on efficacy but even more importantly on safety in patients with heart failure and preserved and impaired ventricular function.…”