Ranolazine Exerts Potent Effects on Atrial Electrical Properties and Abbreviates Atrial Fibrillation Duration in the Intact Porcine Heart

Kumar, Kapil; Nearing, Bruce D.; Carvas, Marcelo; Nascimento, Bruno; Acar, Mariana; Belardinelli, Luiz; Ph.D., F.A.C.C. Richard L. Verrier

doi:10.1111/j.1540-8167.2009.01437.x

Cited by 99 publications

(88 citation statements)

References 26 publications

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“…S5; inhibition for Phe and 3,4,5-F 3 -Phe not significantly different at 20 Hz; P > 0.2). It is important to note that ranolazine, although a direct derivative of lidocaine, no longer displays class Ib-like characteristics as it prolongs the APD and increases the ERP 37,38 . In contrast, we observed an energetically significant cationpi interaction with Phe 1760 for 2-(dimethylamino)ethyl benzoate (DMAE-B) (Fig.…”

Section: Resultsmentioning

confidence: 99%

Molecular basis for class Ib anti-arrhythmic inhibition of cardiac sodium channels

et al. 2011

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Cardiac sodium channels are established therapeutic targets for the management of inherited and acquired arrhythmias by class I anti-arrhythmic drugs (AADs). These drugs share a common target receptor bearing two highly conserved aromatic side chains, and are subdivided by the Vaughan-Williams classification system into classes Ia-c based on their distinct effects on the electrocardiogram. How can these drugs elicit distinct effects on the cardiac action potential by binding to a common receptor? Here we use fluorinated phenylalanine derivatives to test whether the electronegative surface potential of aromatic side chains contributes to inhibition by six class I AADs. Surprisingly, we find that class Ib AADs bind via a strong electrostatic cation-pi interaction, whereas class Ia and Ic AADs rely significantly less on this interaction. Our data shed new light on drug-target interactions underlying the inhibition of cardiac sodium channels by clinically relevant drugs and provide information for the directed design of AADs.

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Section: Resultsmentioning

confidence: 99%

Molecular basis for class Ib anti-arrhythmic inhibition of cardiac sodium channels

et al. 2011

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“…Additionally, ranolazine can be used on top of class III drugs as it has been shown that it does not cause pro‐arrhythmia despite a marked effect on ventricular repolarization 48, 49, 50. The beneficial role of ranolazine has also been demonstrated by experimental and human studies in atrial arrhythmias 10, 44, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61…”

Section: Discussionmentioning

confidence: 99%

Impact of ranolazine on ventricular arrhythmias – A systematic review

Bazoukis

Tse

Letsas

et al. 2018

Journal of Arrhythmia

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Ranolazine is a new medication for the treatment of refractory angina. However, except its anti‐anginal properties, it has been found to act as an anti‐arrhythmic. The aim of our systematic review is to present the existing data about the impact of ranolazine in ventricular arrhythmias. We searched MEDLINE and Cochrane databases as well clinicaltrials.gov until September 1, 2017 to find all studies (clinical trials, observational studies, case reports/series) reported data about the impact of ranolazine in ventricular arrhythmias. Our search revealed 14 studies (3 clinical trials, 2 observational studies, 8 case reports, 1 case series). These data reported a beneficial impact of ranolazine in ventricular tachycardia/fibrillation, premature ventricular beats, and ICD interventions in different clinical settings. The existing data highlight the anti‐arrhythmic properties of ranolazine in ventricular arrhythmias.

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“…Ranolazine has been proposed to exert inhibitory effects on atrial sodium channel parameters as well as on the delayed rectifier potassium current (I Kr ) slightly prolonging the atrial action potential [3]. This probably explains an increased effective refractory period (to a greater extent than in the ventricle) and prolonged atrial conduction time in a frequency-dependent manner in the porcine heart [4]. One major problem regarding the pharmacological treatment of atrial fibrillation using peak I Na blockers is ventricular proarrhythmia.…”

Section: Discussionmentioning

confidence: 99%

Ranolazine Maintained Sinus Rhythm in a Patient with Refractory Symptomatic Atrial Fibrillation

Sossalla

Sohns

Seegers

et al. 2013

Cardiovascular Therapeutics

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SUMMARYWe report on a patient who was treated with several antiarrhythmic drugs as well as different ablation strategies. Nevertheless, symptomatic atrial fibrillation always recurred until an off-label use with ranolazine was started. We could demonstrate potent effects of ranolazine on atrial fibrillation in a "wash-in wash-out" situation. Although promising controlled studies are needed to investigate a potential role of ranolazine for the treatment of atrial fibrillation.

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Ranolazine Exerts Potent Effects on Atrial Electrical Properties and Abbreviates Atrial Fibrillation Duration in the Intact Porcine Heart

Cited by 99 publications

References 26 publications

Molecular basis for class Ib anti-arrhythmic inhibition of cardiac sodium channels

Molecular basis for class Ib anti-arrhythmic inhibition of cardiac sodium channels

Impact of ranolazine on ventricular arrhythmias – A systematic review

Ranolazine Maintained Sinus Rhythm in a Patient with Refractory Symptomatic Atrial Fibrillation

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