Investigational Drug Details
| Drug ID: | D298 |
| Drug Name: | Ranolazine |
| Synonyms: | Ranolazine |
| Type: | Chemical drug |
| DrugBank ID: | DB00243 |
| DrugBank Description: | Chronic angina is a common cardiovascular condition affecting millions worldwide and causes significant disability while interfering with daily activities. Ranolazine is a well-tolerated piperazine derivative used for the management of this condition, offering relief from uncomfortable and debilitating symptoms. With a mechanism of action different from drugs used to treat the same condition, ranolazine is a promising anti-anginal therapy. It was originally approved by the FDA in 2006. |
| PubChem ID: | 56959 |
| CasNo: | 95635-55-5 |
| Repositioning for NAFLD: | Yes |
| SMILES: | O(CC(CN1CCN(CC1)CC(=O)Nc1c(C)cccc1C)O)c1c(OC)cccc1 |
| Structure: |
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| InChiKey: | XKLMZUWKNUAPSZ-UHFFFAOYSA-N |
| Molecular Weight: | 427.545 |
| DrugBank Targets: | Sodium channel protein inhibitor; Inward rectifier potassium channel inhibitor; Voltage gated L-type calcium channel inhibitor; Alpha-1 adrenergic receptors antagonist; Beta-1 adrenergic receptor antagonist; Fatty acid other/unknown |
| DrugBank MoA: | Myocardial ischemia exerts effects on adenosine triphosphate flux, leading to a decrease in the energy available for contraction and relaxation of the heart muscle. Electrolyte balance of sodium and potassium is necessary for maintaining normal cardiac contraction and relaxation. Disruption of adequate sodium and potassium electrolyte balance leads to excessively high concentrations of sodium and calcium, which likely interferes with oxygen supply to the heart muscle. This imbalance eventually leads to angina symptoms of chest pain or pressure, nausea, and dizziness, among others. The mechanism of action for ranolazine is not fully understood. At therapeutic concentrations, it can inhibit the cardiac late sodium 205 current (INa), which may affect the electrolyte balance in the myocardium, relieving angina symptoms. The clinical significance this inhibition in the treatment of angina symptoms is not yet confirmed. Ranolazine inhibits sodium and potassium ion channel currents. It has been shown to exert weak activity on L-type calcium channels making it a weak direct vasodilator and exerts minimal direct effects on atrioventricular nodal conduction. Some additional mechanisms have been elucidated. Ranolazine exerts antagonistic activity towards the alpha 1 and beta 1 adrenergic receptors and inhibition of fatty acid oxidation. |
| DrugBank Pharmacology: | Ranolazine exerts both antianginal and ischemic effects independent from lowering heart rate or blood pressure. It blocks IKr, the rapid portion of the delayed rectifier potassium current, and prolongs the QTc interval in a dose-dependent fashion. The Ikr is important for cardiac repolarization. Ranolazine exerts its therapeutic effects without negative chronotropic, dromotropic, or inotropic actions neither at rest, nor during exercise. |
| DrugBank Indication: | Ranolazine is indicated for the treatment of chronic angina. It can be used alone or in conjunction with nitrates, beta-blockers, angiotensin receptor blockers, anti-platelet drugs, calcium channel blockers, lipid-lowering drugs, and ACE inhibitors. Ranolazine has also been used off-label for the treatment of certain arrhythmias, including ventricular tachycardia, however, this use is not strongly supported by scientific evidence. Ranolazine has also been studied for the treatment of acute coronary syndrome, microvascular coronary dysfunction, arrhythmia, and glycemic control, which are not yet approved indications. |
| Targets: | -- |
| Therapeutic Category: | -- |
| Clinical Trial Progress: | Phase 4 on-going (CTRI/2019/06/019592) |
| Latest Progress: | Under clinical trials |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L0742 | CTRI/2019/06/019592 | Phase 4 | Recruiting | No Results Available | 10/06/2019 | 24 November 2021 | Details |
| Article ID | PMID | Source | Title | |
|---|---|---|---|---|
| A01153 | 34851748 | Can J Physiol Pharmacol | The anti-anginal ranolazine does not confer beneficial actions against hepatic steatosis in male mice subjected to high-fat diet and streptozotocin-induced type 2 diabetes. | Details |
| A03907 | 33823622 | Angiology | Evaluation of the Impact of Ranolazine Treatment on Liver Function Tests in Patients With Coronary Heart Disease and Nonalcoholic Fatty Liver Disease. | Details |
| A12042 | 30626749 | JCI Insight | The antianginal ranolazine mitigates obesity-induced nonalcoholic fatty liver disease and increases hepatic pyruvate dehydrogenase activity. | Details |
| A42672 | 33827290 | Angiology | The Impact of Ranolazine Treatment on Liver Tests in Patients With Coronary Artery Disease and Nonalcoholic Fatty Liver Disease. | Details |