Repositioning Candidate Details
| Candidate ID: | R0431 |
| Source ID: | DB04861 |
| Source Type: | approved; investigational |
| Compound Type: | small molecule |
| Compound Name: | Nebivolol |
| Synonyms: | |
| 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.[A182579] Treatment with nebivolol leads to a greater decrease in systolic and diastolic blood pressure than [atenolol], [propranolol], or [pindolol].[A182579] Nebivolol and other beta blockers are generally not first line therapies as many patients are first treated with thiazide diuretics.[A182594] Nebivolol was granted FDA approval on 17 December 2007.[L7985] |
| CAS Number: | 118457-14-0 |
| Molecular Weight: | 405.435 |
| DrugBank Indication: | Nebivolol is indicated to treat hypertension.[A2762,A182579,L7985,L7988] |
| 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.[A182579,A182585] 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.[A182579,L7985] Patients should not abruptly stop taking this medication as this may lead to exacerbation of coronary artery disease.[L7985] Diabetic patients should monitor their blood glucose levels as beta blockers may mask signs of hypoglycemia.[L7985] |
| DrugBank MoA: | Nebivolol is a highly selective beta-1 adrenergic receptor antagonist[A182579] with weak beta-2 adrenergic receptor antagonist activity.[A182585] 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.[A182603,A182579,A182585,A182615] The selectivity of d-nebivolol limits the magnitude of beta blocker adverse effects in the airways or relating to insulin sensitivity.[A182615] Nebivolol also inhibits aldosterone, and beta-1 antagonism in the juxtaglomerular apparatus also inhibits the release of renin.[A182615] Decreased aldosterone leads to decreased blood volume, and decreased renin leads to reduced vasoconstriction.[A182615] 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.[A2762,A182603,A182579,A182585,A182615] The vasodilation, reduced oxidative stress, and reduced platelet volume and aggregation of nebivolol may lead to benefits in heart failure patients.[A182603] |
| Targets: | Beta-1 adrenergic receptor; Beta-2 adrenergic receptor; Beta-3 adrenergic receptor |
| Inclusion Criteria: |
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