Through the heart and beyond: a review on ranolazine

Uran, Carlo

doi:10.4081/monaldi.2021.1806

Cited by 3 publications

(2 citation statements)

References 64 publications

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“…The selective I Na inhibitor ranolazine is approved for symptomatic treatment of stable angina ( Silva et al, 2016 ). In animal models of HF, ranolazine effectively lowered [Na + ] i , improved diastolic function, prevented arrhythmias, and pulmonary hypertension ( Uran, 2021 ). On these grounds, ranolazine was tested in patients with HF with preserved ejection fraction, but did not affect ventricular relaxation in the RALI-DHF trial (Ranolazine in Diastolic HF) ( Maier et al, 2013 ).…”

Section: Mitochondrial Ca 2+ Handling As a Therape...mentioning

confidence: 99%

Mitochondrial calcium signaling and redox homeostasis in cardiac health and disease

Popoiu,

Maack,

Bertero

2023

Front. Mol. Med

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The energy demand of cardiomyocytes changes continuously in response to variations in cardiac workload. Cardiac excitation-contraction coupling is fueled primarily by adenosine triphosphate (ATP) production by oxidative phosphorylation in mitochondria. The rate of mitochondrial oxidative metabolism is matched to the rate of ATP consumption in the cytosol by the parallel activation of oxidative phosphorylation by calcium (Ca2+) and adenosine diphosphate (ADP). During cardiac workload transitions, Ca2+ accumulates in the mitochondrial matrix, where it stimulates the activity of the tricarboxylic acid cycle. In this review, we describe how mitochondria internalize and extrude Ca2+, the relevance of this process for ATP production and redox homeostasis in the healthy heart, and how derangements in ion handling cause mitochondrial and cardiomyocyte dysfunction in heart failure.

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Section: Mitochondrial Ca 2+ Handling As a Therape...mentioning

confidence: 99%

Mitochondrial calcium signaling and redox homeostasis in cardiac health and disease

Popoiu,

Maack,

Bertero

2023

Front. Mol. Med

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“…Ranolazine (RAN) is an antianginal drug that has been studied for several purposes [6]. RAN prevents the increase in Na + by blocking late Na + channels and the accumulation of cellular Ca 2+ through Na/Ca 2+ exchange (NCX) and restores mitochondrial function, thereby exerting an antioxidant effect by preventing the formation of ROS [7,8].…”

Section: Introductionmentioning

confidence: 99%

Ranolazine reduces oxidative damage and improves kidney function in cisplatin-induced nephrotoxicity

Tanriverdi,

Goncu,

Gunata

et al. 2023

Preprint

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Cisplatin (CIS)-induced nephrotoxicity is associated with oxidative stress, apoptosis, inflammation, and fibrogenesis. In this study, we investigated the therapeutic effects of ranolazine (RAN), a current antianginal drug known to experimentally reduce oxidative damage in CIS-induced nephrotoxicity. We randomly assigned thirty-two Sprague Dawley rats to one of four groups (Control, CIS, CIS+RAN, and RAN+CIS). We evaluated kidney function parameters including blood urea nitrogen (BUN), creatinine (Cre), electrolytes, and albumin, as well as tissue biochemical parameters including malondialdehyde (MDA) and antioxidant enzymes. Histopathological parameters were also assessed. We observed a significant increase in BUN and Cre values in the CIS group compared to the control group (p<0.05). However, there was a significant decrease in BUN values (p<0.05) in the CIS+RAN and RAN+CIS groups compared to the CIS group. In contrast, the decrease in Cre values did not reach statistical significance (p>0.05), and serum electrolytes were comparable among groups. Furthermore, a statistically significant increase in albumin levels was observed in the CIS+RAN group compared to the CIS group (p<0.05). MDA levels were significantly decreased in the CIS+RAN group compared to the CIS group, indicating the antioxidant activity of RAN (p<0.05). Histopathological analysis revealed that necrosis and dilatation in epithelial cells of cortical and medullary tubules were more prominent in the CIS group (p<0.0001). However, in the RAN+CIS group, the histopathological changes observed in the CIS group were found to be significantly reduced (p<0.0001). Degenerative changes in tubules were observed in the CIS+RAN group (p>0.05). Our findings suggest that the beneficial effects of RAN on CIS-induced nephrotoxicity may be related to its antioxidant activity.

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Ranolazine Interacts Antagonistically with Some Classical Antiepileptic Drugs—An Isobolographic Analysis

Borowicz-Reutt

Banach

2022

Molecules

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Ranolazine, an antianginal and antiarrhythmic drug blocking slow inactivating persistent sodium currents, is described as a compound with anticonvulsant potential. Since arrhythmia often accompanies seizures, patients suffering from epilepsy are frequently co-treated with antiepileptic and antiarrhythmic drugs. The aim of this study was to evaluate the effect of ranolazine on maximal-electroshock (MES)-induced seizures in mice as well as interactions between ranolazine and classical antiepileptic drugs in this model of epilepsy. Types of pharmacodynamic interactions were established by isobolographic analysis of obtained data. The main findings of the study were that ranolazine behaves like an antiseizure drug in the MES test. Moreover, ranolazine interacted antagonistically with carbamazepine, phenytoin, and phenobarbital in the proportions of 1:3 and 1:1. These interactions occurred pharmacodynamic, since ranolazine did not change the brain levels of antiepileptic drugs measured in the fluorescence polarization immunoassay. Ranolazine and its combinations with carbamazepine, phenytoin, and phenobarbital did not impair motor coordination evaluated in the chimney test. Unfortunately, an attempt to conduct a passive avoidance task (evaluating long-term memory) resulted in ranolazine-induced delayed lethality. In conclusion, ranolazine exhibits clear-cut anticonvulsant properties in the MES test but interacts antagonistically with some antiepileptic drugs. The obtained results need confirmation in clinical studies. The mechanisms of ranolazine-induced toxicity require specific explanation.

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Through the heart and beyond: a review on ranolazine

Cited by 3 publications

References 64 publications

Mitochondrial calcium signaling and redox homeostasis in cardiac health and disease

Mitochondrial calcium signaling and redox homeostasis in cardiac health and disease

Ranolazine reduces oxidative damage and improves kidney function in cisplatin-induced nephrotoxicity

Ranolazine Interacts Antagonistically with Some Classical Antiepileptic Drugs—An Isobolographic Analysis

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