Antiarrhythmic drugs: new agents and evolving concepts

Němec, Jan; Shen, Win Kuang

doi:10.1517/13543784.12.3.435

Expert Opinion on Investigational Drugs

2003

DOI: 10.1517/13543784.12.3.435

|View full text |Cite

Antiarrhythmic drugs: new agents and evolving concepts

Jan Němec

Win Kuang Shen

Abstract: Properties of several new antiarrhythmic drugs are summarised in this review article. Recent concepts concerning their safety and efficacy of antiarrhythmics are discussed. A brief perspective on possible future strategies for pharmacotherapy of arrhythmias is provided.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2005

2007

Publication Types

Select...

Article5

Relationship

Self Cite0

Independent5

Authors

Journals

Cited by 6 publications

References 161 publications

(89 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

Calcium Antagonist Property of Cpu228, a Dofetilide Derivative, Contributes to Its Low Incidence of Torsades De Pointes in Rabbits

Huang

Dai

et al. 2007

Clin Exp Pharma Physio

View full text Add to dashboard Cite

1. Torsades de pointes (TDP) is a severe adverse effect during the clinical use of dofetilide, a selective blocker of the rapid component of the delayed rectifier potassium channel (I(Kr)). The present study was designed to test whether CPU228, a derivative of dofetilide with calcium (Ca(2+)) antagonist properties, could reduce TDP without reducing the blockade of I(Kr). 2. The incidence of TDP in a rabbit model and the effective refractory period (ERP) were measured and compared for dofetilide and CPU228. Suppression of I(Kr) and the L-type Ca(2+) current (I(Ca,L)) and the Ca(2+) transients of isolated cardiomyocytes were investigated by whole-cell patch-clamp and Fluo-3 dye spectrophotometry. 3. The incidence of TDP was greatly reduced by CPU228 relative to dofetilide, occurring in only one of six rabbits compared with five of six rabbits following dofetilide (P < 0.05). In isolated atria, prolongation of ERP by CPU228 was less than that of dofetilide and no reverse frequency dependence was observed. Negative inotropism by CPU228 was significant against positive inotropism by dofetilide. CPU228 inhibited both I(Kr) and I(Ca,L) currents and the IC(50) for I(Ca,L) inhibition was 0.909 micromol/L. At 3 micromol/L, CPU228 significantly suppressed the Ca(2+) transients. 4. CPU228 is able to block I(Ca,L), contributing to decreased TDP, while also blocking I(Kr) activity. By combined blockade of I(Kr) and I(Ca,L), CPU228 shares the property of complex Class III anti-arrhythmic agents.

show abstract

Calcium Antagonist Property of Cpu228, a Dofetilide Derivative, Contributes to Its Low Incidence of Torsades De Pointes in Rabbits

Huang

Dai

et al. 2007

Clin Exp Pharma Physio

View full text Add to dashboard Cite

show abstract

Inappropriate Sinus Tachycardia, Postural Orthostatic Tachycardia Syndrome, and Overlapping Syndromes

Brady

Low

Shen

2005

Pacing Clinical Electrophis

View full text Add to dashboard Cite

show abstract

Ion channelopathy and hyperphosphorylation contributing to cardiac arrhythmias1

Dai

Feng

2005

Acta Pharmacologica Sinica

View full text Add to dashboard Cite

The occurrence of cardiac arrhythmias is related to the abnormality of ion channels not only in sarcolemma but also in the sarcoplasmic reticulum, which regulates the process of calcium release and up‐take intracellularly. Patterns of ion channelopathy in the sarcolemma can be divided into single channel disorder from gene mutations and multiple channels disorder in a diseased hypertrophied heart. Abnormal RyR2, FKBP12.6, SERCA2a, and PLB are also involved in the initiation of cardiac arrhythmias. Maladjustment by hyperphosphorylation on the ion channels in the sarcolemma and RyR2‐FKBP12.6 and SERCA2a‐PLB is discussed. Hyperphosphorylation, which is the main abnormality upstream to ion channels, can be targeted for suppressing the deterioration of ion channelopathy in terms of new drug discovery in the treatment and prevention of malignant cardiac arrhythmias.

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

hi@scite.ai

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Antiarrhythmic drugs: new agents and evolving concepts

Abstract: Properties of several new antiarrhythmic drugs are summarised in this review article. Recent concepts concerning their safety and efficacy of antiarrhythmics are discussed. A brief perspective on possible future strategies for pharmacotherapy of arrhythmias is provided.

Cited by 6 publications

References 161 publications

Calcium Antagonist Property of Cpu228, a Dofetilide Derivative, Contributes to Its Low Incidence of Torsades De Pointes in Rabbits

Calcium Antagonist Property of Cpu228, a Dofetilide Derivative, Contributes to Its Low Incidence of Torsades De Pointes in Rabbits

Inappropriate Sinus Tachycardia, Postural Orthostatic Tachycardia Syndrome, and Overlapping Syndromes

Ion channelopathy and hyperphosphorylation contributing to cardiac arrhythmias1

Contact Info

Product

Resources

About