Ranolazine:an Antiischemic Drug with a Novel Mechanism of Action

Hara, Akiyoshi; Matsumura, Hisao; Maruyama, Kazuyasu; Hashizume, Hiroko; Ushikubi, Fumitaka; Abiko, Yasushi

doi:10.1111/j.1527-3466.1999.tb00004.x

Cited by 5 publications

(2 citation statements)

References 58 publications

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“…Trimetazidine is likely to stimulate carbohydrate oxidation by directly inhibiting theoxidation of fatty acids and secondarily activating PDH (Hara et al, 1999).…”

Section: Trimetazidinementioning

confidence: 99%

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Metabolic Modulators to Treat Cardiac Arrhythmias Induced by Ischemia and Reperfusion

Najafi¹,

Eteraf-Oskouei²

2012

Tachycardia

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“…Trimetazidine is likely to stimulate carbohydrate oxidation by directly inhibiting theoxidation of fatty acids and secondarily activating PDH (Hara et al, 1999).…”

Section: Trimetazidinementioning

confidence: 99%

“…DCA is a PDH activator (Liu et al, 2002) and stimulates carbohydrate oxidation through direct inhibition of PDH kinase and reduces fatty acid oxidation through inhibition of fatty acid uptake by mitochondria (Hara et al, 1999).…”

Section: Dichloroacetate (Dca)mentioning

confidence: 99%

Metabolic Modulators to Treat Cardiac Arrhythmias Induced by Ischemia and Reperfusion

Najafi¹,

Eteraf-Oskouei²

2012

Tachycardia

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Medical Therapy for Chronic Right Ventricular Failure in Congenital Heart Disease

Roche

2017

Right Ventricular Physiology, Adaptation and Failure in Congenital and Acquired Heart Disease

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Evidence that ranolazine behaves as a weak β 1 - and β 2 -adrenoceptor antagonist in the rat cardiovascular system

Létienne

Vié

Puech

et al. 2001

Naunyn-Schmiedeberg's Archives of Pharmacology

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The clinical anti-anginal effectiveness of ranolazine is currently being evaluated. However, the mechanism of its anti-ischaemic action is still unclear. The aim of this work was to establish whether ranolazine exerts functional beta-adrenoceptor antagonist activity in the rat cardiovascular system. Radioligand binding studies were performed in rat hearts and guinea-pig lungs for beta1- and beta2-adrenoceptor affinity, respectively. Ranolazine had micromolar affinity for both beta,- and beta2-adrenoceptors (pKi5.8 and 6.3, respectively). Developed tension was measured in isolated rat left atria (electrically driven at 4 Hz) and cumulative concentration/response curves to (+/-)isoprenaline (0.01-1,000 nM) constructed. Ranolazine (0.32-10 microM) surmountably but weakly antagonised isoprenaline-induced positive inotropic responses, with an apparent pA2 of 5.85 (5.69-6.00) and a slope of -0.74 (-0.70 to -0.77). In bivagotomised, atropinised pithed rats, ranolazine per se evoked marked bradycardia at doses above 10 mg/kg i.v. (maximum variation at 80 mg/kg -125+/-15 bpm, n=6, P<0.001) by a mechanism apparently unrelated to blockade of beta1- or beta2-adrenoceptors. Cumulative incremental doses of (+/-)isoprenaline (0.63 ng/kg to 0.16 mg/kg i.v.) administered to pithed rats induced concomitant depressor and chronotropic responses. Animals received either vehicle (saline 0.9% i.v., n=12), atenolol (0.04-2.5 mg/kg i.v., n=6 per dose), ICI 118551 (0.01-0.63 mg/kg i.v., n=6 or 7 per dose), (+/-)propranolol (0.01-0.63 mg/kg i.v., n=6 per dose) or ranolazine (2.5-80 mg/kg i.v., n=6 or 7 per dose) 10 min prior to isoprenaline. Ranolazine dose-dependently and competitively antagonised isoprenaline-induced decreases in diastolic arterial pressure (DAP, dose ratio 12.2 with 80 mg/kg ranolazine) and increases in heart rate (HR, dose ratio 20.3 with 80 mg/kg ranolazine). Collectively, these results demonstrate that ranolazine behaves as a weak beta1- and beta2-adrenoceptor antagonist in the rat cardiovascular system.

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Ranolazine:an Antiischemic Drug with a Novel Mechanism of Action

Cited by 5 publications

References 58 publications

Metabolic Modulators to Treat Cardiac Arrhythmias Induced by Ischemia and Reperfusion

Metabolic Modulators to Treat Cardiac Arrhythmias Induced by Ischemia and Reperfusion

Medical Therapy for Chronic Right Ventricular Failure in Congenital Heart Disease

Evidence that ranolazine behaves as a weak β 1 - and β 2 -adrenoceptor antagonist in the rat cardiovascular system

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