Repositioning Candidate Details
| Candidate ID: | R0629 |
| Source ID: | DB04861 |
| Source Type: | approved; investigational |
| Compound Type: | small molecule |
| Compound Name: | Nebivolol |
| Synonyms: | Narbivolol; Nebivolol |
| Molecular Formula: | C22H25F2NO4 |
| SMILES: | OC(CNCC(O)C1CCC2=C(O1)C=CC(F)=C2)C1CCC2=C(O1)C=CC(F)=C2 |
| Structure: |
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| DrugBank Description: | Nebivolol is a racemic mixture of 2 enantiomers where one is a beta adrenergic antagonist and the other acts as a cardiac stimulant without beta adrenergic activity. Treatment with nebivolol leads to a greater decrease in systolic and diastolic blood pressure than , , or . Nebivolol and other beta blockers are generally not first line therapies as many patients are first treated with thiazide diuretics. Nebivolol was granted FDA approval on 17 December 2007. |
| CAS Number: | 118457-14-0 |
| Molecular Weight: | 405.435 |
| DrugBank Indication: | Nebivolol is indicated to treat hypertension. |
| DrugBank Pharmacology: | Nebivolol is a selective beta-1 adrenergic receptor antagonist that decreases vascular resistance, increases stroke volume and cardiac output, and does not negatively affect left ventricular function. It has a long duration of action as effects can be seen 48 hours after stopping the medication and a wide therapeutic window as patients generally take 5-40mg daily. Patients should not abruptly stop taking this medication as this may lead to exacerbation of coronary artery disease. Diabetic patients should monitor their blood glucose levels as beta blockers may mask signs of hypoglycemia. |
| DrugBank MoA: | Nebivolol is a highly selective beta-1 adrenergic receptor antagonist with weak beta-2 adrenergic receptor antagonist activity. Blocking beta-1 adrenergic receptors by d-nebivolol leads to decreased resting heart rate, exercise heart rate, myocardial contracility, systolic blood pressure, and diastolic blood pressure. The selectivity of d-nebivolol limits the magnitude of beta blocker adverse effects in the airways or relating to insulin sensitivity. Nebivolol also inhibits aldosterone, and beta-1 antagonism in the juxtaglomerular apparatus also inhibits the release of renin. Decreased aldosterone leads to decreased blood volume, and decreased renin leads to reduced vasoconstriction. l-nebivolol is responsible for beta-3 adrenergic receptor agonist activity that stimulates endothelial nitric oxide synthase, increasing nitric oxide levels; leading to vasodilation, decreased peripheral vascular resistance, increased stroke volume, ejection fraction, and cardiac output. The vasodilation, reduced oxidative stress, and reduced platelet volume and aggregation of nebivolol may lead to benefits in heart failure patients. |
| Targets: | Beta-1 adrenergic receptor antagonist; Beta-2 adrenergic receptor antagonist; Beta-3 adrenergic receptor agonist |
| Inclusion Criteria: | Therapeutic strategy associated |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I16 | 6713 | Cerebrovascular disease | An vascular disease that is characterized by dysfunction of the blood vessels supplying the brain. http://en.wikipedia.org/wiki/Cerebrovascular_disease, http://www.ncbi.nlm.nih.gov/books/NBK378/ | disease of anatomical entity/ cardiovascular system disease/ vascular disease/cerebrovascular disease | Details |
| I12 | 10763 | Hypertension | An artery disease characterized by chronic elevated blood pressure in the arteries. https://en.wikipedia.org/wiki/Hypertension, https://www.ncbi.nlm.nih.gov/pubmed/24352797 | disease of anatomical entity/ cardiovascular system disease/vascular disease/ artery disease | Details |