Azimilide Dihydrochloride, a Novel Antiarrhythmic Agent

Karam, Roger; Marcello, Stephen; Brooks, Robert R.; Corey, A.; Moore, Alan

doi:10.1016/s0002-9149(98)00152-0

Cited by 71 publications

(31 citation statements)

References 13 publications

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“…Some reports showed that azimilide, like amiodarone, possesses calcium and use-dependent sodium channel blocking effects [38,39]. However, we must emphasize that after some encouraging studies in AF [40,41], the initial optimism disappeared and the modest results of several studies (e.g., the ALIVE study) ended up with the conclusion that azimilide will never become a powerful tool for treating AF [42,43].…”

Section: Selective I Ks Blockersmentioning

confidence: 99%

Atrial Remodeling in Permanent Atrial Fibrillation: Mechanisms and Pharmacological Implications

Muntean¹,

Kohajda²,

Fazekas

et al. 2013

J Clin Exp Cardiolog

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Atrial fibrillation (AF), the most prevalent rhythm disorder in clinical practice, is currently significantly contributing to morbidity and mortality of the ageing population. In the past decades, a tremendous amount of research resulted in valuable insights into AF pathophysiology, with a primary focus on atrial remodeling. Defined as a persistent change in atrial function and structure, remodeling has the intrinsic properties to enhance the probability of focal (ectopic) and/or re-entrant pursuits, thus supporting AF persistence. The hallmark of structural remodeling is represented by atrial fibrosis, a multifactorial process involving an interaction between neurohormonal and cellular mediators. This paper provides a brief summary of the recent knowledge with respect to electrical and structural remodeling and novel insights into the pathogenesis of atrial fibrosis. Since current drug options for AF treatment are far from being optimal we also discuss the therapeutic principles and current alternatives for counteracting atrial fibrosis, and thus preventing arrhythmia recurrence.

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Section: Selective I Ks Blockersmentioning

confidence: 99%

Atrial Remodeling in Permanent Atrial Fibrillation: Mechanisms and Pharmacological Implications

Muntean¹,

Kohajda²,

Fazekas

et al. 2013

J Clin Exp Cardiolog

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“…Dofetilide's proarrhythmic potential, which prompted the FDA to require in-hospital initiation of therapy [Al-Dashti and Sami, 2001], limits the usefulness of this drug. As with highly selective I Kr blockers, development of highly selective blockers of the slow component of the delayed rectifier (I Ks ) [Yang et al, 2000] has largely been abandoned with the exception of the nonselective delayed rectifier blocker, azimilide, which is awaiting regulatory approval [Karam et al, 1998]. Aventis has not commenced clinical testing of its selective I Ks blocker, HMR1556 [Gogelein et al, 2000], whereas Merck appears to have terminated its I Ks blocker program [Selnick et al, 1997].…”

Section: Selective Delayed Rectifier Blockersmentioning

confidence: 99%

Ventricular fibrillation, an uncontrolled arrhythmia seeking new targets

Beatch

Barrett

Plouvier

et al. 2002

Drug Development Research

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Ventricular antiarrhythmic drugs in current clinical use leave much to be desired in terms of safety and efficacy. With the exception of beta-adrenoreceptor blockers, none of the available antiarrhythmic drugs have significantly improved survival after myocardial infarction. Amiodarone has shown marginal benefit but has several safety limitations. As a result, there is a large unmet medical need for a safe and effective drug to treat lethal ventricular arrhythmias. Despite the difficulties in developing such a drug, there are a few research programs dedicated to solving this unmet medical need. These include drugs that are targeted to the pathological substrate responsible for initiating arrhythmias and drugs that block multiple ion channels in a manner similar to amiodarone. A few research programs are directed toward other molecular targets. This article briefly reviews the active research programs in the pharmaceutical industry currently that are pursuing ventricular antiarrhythmic drugs. Drug Dev. Res. 55:45-52, 2002.

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“…Unlike conventional potassium channel blockers such as sotalol and dofetilide, which block only slowly activating (I Ks ) components of the delayed rectifier potassium current of human atrial and ventricular myocytes, azimilide blocks both the I Ks and rapidly activating (I Kr ) components. 1 Azimilide dihydrochloride (75-125 mg/day) is currently being developed for use in prolonging the time to recurrence of atrial fibrillation/flutter and for reducing the frequency of shocks in patients with an implantable cardioverting defibrillator.…”

Section: Introductionmentioning

confidence: 99%

“…2 Following intravenous administration, azimilide pharmacokinetic parameters include: total clearance ¼ 0.136 L/h/kg; renal clearance (CL r ) ¼ 0.013 L/h/kg; steady-state volume of distribution ¼ 12.9 L/kg; and a terminal exponential halflife ¼ 71.4 h. Azimilide plasma protein binding is about 94%, 3 is concentration independent over the range observed clinically and is predominately bound to albumin, with minor binding to alpha 1 acid glycoprotein. 4,5 These parameters indicate that azimilide has a low extraction ratio (low capacity clearance) with a steady-state volume of distribution consistent with extensive tissue distribution.…”

Section: Introductionmentioning

confidence: 99%