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The antiarrhythmic drug BRL-32872.
Cardiovasc Drug Rev. 2002 Summer; 20(2):111-20.CD

Abstract

BRL-32872 is a new antiarrhythmic drug with balanced class-III and class-IV actions as categorized by the Vaughan-Williams classification. BRL-32872 blocks the rapid component of the cardiac delayed rectifier potassium channel IK(r) (IC(50) = 28 nM) and its molecular correlate HERG ("Human-ether-a-go-go related gene," IC(50) of 19.8 nM in cell lines) at low concentrations. It also inhibits the L-type calcium current (ICa) at higher concentrations (IC(50) = 2.8 microM). This dual concentration-dependent profile of action at higher concentrations may possibly prevent "torsades de pointes" ventricular arrhythmias, which is a dangerous side effect of many other class-III antiarrhythmic drugs. With BRL-32872, an excessive prolongation of the action potential duration and consecutive QTc prolongation is prevented by a concentration-dependent increase of calcium channel block, resulting in the so-called "bell-shaped" profile of antiarrhythmic drug action. BRL-32872 is very effective in the treatment of ventricular arrhythmias in animal models of cardiac ischemia. In the ischemic hearts of animals the drug significantly reduced early afterdepolarization and ventricular tachycardia. The antiarrhythmic effect of BRL-32872 has not yet been demonstrated in humans.

Authors+Show Affiliations

Department of Cardiology, Medical University Hospital Heidelberg, Heidelberg, Germany.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

12177689

Citation

Karle, Christoph A., et al. "The Antiarrhythmic Drug BRL-32872." Cardiovascular Drug Reviews, vol. 20, no. 2, 2002, pp. 111-20.
Karle CA, Thomas D, Kiehn J. The antiarrhythmic drug BRL-32872. Cardiovasc Drug Rev. 2002;20(2):111-20.
Karle, C. A., Thomas, D., & Kiehn, J. (2002). The antiarrhythmic drug BRL-32872. Cardiovascular Drug Reviews, 20(2), 111-20.
Karle CA, Thomas D, Kiehn J. The Antiarrhythmic Drug BRL-32872. Cardiovasc Drug Rev. 2002;20(2):111-20. PubMed PMID: 12177689.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The antiarrhythmic drug BRL-32872. AU - Karle,Christoph A, AU - Thomas,Dierk, AU - Kiehn,Johann, PY - 2002/8/15/pubmed PY - 2002/11/26/medline PY - 2002/8/15/entrez SP - 111 EP - 20 JF - Cardiovascular drug reviews JO - Cardiovasc Drug Rev VL - 20 IS - 2 N2 - BRL-32872 is a new antiarrhythmic drug with balanced class-III and class-IV actions as categorized by the Vaughan-Williams classification. BRL-32872 blocks the rapid component of the cardiac delayed rectifier potassium channel IK(r) (IC(50) = 28 nM) and its molecular correlate HERG ("Human-ether-a-go-go related gene," IC(50) of 19.8 nM in cell lines) at low concentrations. It also inhibits the L-type calcium current (ICa) at higher concentrations (IC(50) = 2.8 microM). This dual concentration-dependent profile of action at higher concentrations may possibly prevent "torsades de pointes" ventricular arrhythmias, which is a dangerous side effect of many other class-III antiarrhythmic drugs. With BRL-32872, an excessive prolongation of the action potential duration and consecutive QTc prolongation is prevented by a concentration-dependent increase of calcium channel block, resulting in the so-called "bell-shaped" profile of antiarrhythmic drug action. BRL-32872 is very effective in the treatment of ventricular arrhythmias in animal models of cardiac ischemia. In the ischemic hearts of animals the drug significantly reduced early afterdepolarization and ventricular tachycardia. The antiarrhythmic effect of BRL-32872 has not yet been demonstrated in humans. SN - 0897-5957 UR - https://www.unboundmedicine.com/medline/citation/12177689/The_antiarrhythmic_drug_BRL_32872_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0897-5957&date=2002&volume=20&issue=2&spage=111 DB - PRIME DP - Unbound Medicine ER -