Repositioning Candidate Details

Candidate ID: R0346
Source ID: DB00960
Source Type: approved; investigational
Compound Type: small molecule
Compound Name: Pindolol
Synonyms: 1-(1H-indol-4-yloxy)-3-(isopropylamino)propan-2-ol; 1-(1H-indol-4-yloxy)-3-(propan-2-ylamino)-propan-2-ol; 1-(1H-indol-4-yloxy)-3-[(1-methylethyl)amino]propan-2-ol; 4-(2-hydroxy-3-isopropylaminopropoxy)-indole; Pindolol
Molecular Formula: C14H20N2O2
SMILES: CC(C)NCC(O)COC1=CC=CC2=C1C=CN2
Structure:
DrugBank Description: Pindolol is a first generation non-selective beta blocker used in the treatment of hypertension. Early research into the use of pindolol found it had chronotropic effects, and so further investigation focused on the treatment of arrhythmia. Research into pindolol's use in the treatment of hypertension began in the early 1970s. Pindolol was granted FDA approval on 3 September 1982.
CAS Number: 13523-86-9
Molecular Weight: 248.3208
DrugBank Indication: Pindolol is indicated in the management of hypertension. In Canada, it is also indicated in the prophylaxis of angina.
DrugBank Pharmacology: Pindolol is a nonselective beta blocker indicated in the management of hypertension and prophylaxis of angina. It has a short duration of action as it is given twice daily, and a wide therapeutic window as doses can range from 10-60 mg/day. Patients should be counselled regarding the risk of cardiac failure, exacerbating ischemic heart disease with sudden withdrawal, nonallergic bronchospasm, masking hypoglycemia in diabetics, and masking hyperthyroidism.
DrugBank MoA: The beta-1 adrenoceptor is a G-protein-coupled receptor. Agonism of the beta-1 adrenoceptor allows the Gs subunit to upregulate adenylyl cyclase, converting ATP to cyclic AMP (cAMP). Increased concentrations of cAMP activate cAMP-dependant kinase A, phosphorylating calcium channels, raising intracellular calcium, increasing calcium exchange through the sarcoplasmic reticulum, and increasing cardiac inotropy. cAMP-dependant kinase A also phosphorylates myosin light chains, increasing smooth muscle contractility. Increased smooth muscle contractility in the kidney releases renin. Pindolol is a non-selective beta blocker. Blocking beta-1 adrenergic receptors in the heart results in decreased heart rate and blood pressure. By blocking beta-1 receptors in the juxtaglomerular apparatus, pindolol inhibits the release of renin, which inhibits angiotensin II and aldosterone release. Reduced angiotensin II inhibits vasoconstriction and reduced aldosterone inhibits water retention. Beta-2 adrenoceptors located in the kidneys and peripheral blood vessels use a similar mechanism to activate cAMP-dependant kinase A to increase smooth muscle contractility. Blocking of the beta-2 adrenoceptor relaxes smooth muscle, leading to vasodilation.
Targets: Beta-1 adrenergic receptor partial agonist; Beta-2 adrenergic receptor partial agonist; 5-hydroxytryptamine receptor 1A antagonist&inhibitor&ligand; 5-hydroxytryptamine receptor 1B other/unknown&ligand; Beta-3 adrenergic receptor agonist; Beta adrenergic receptor inhibitor
Inclusion Criteria: Indication associated

Strategy ID Strategy Synonyms Related Targets Related Drugs

Target ID Target Name GENE Action Class UniProtKB ID Entry Name
T10 Caspase-1 CASP1 inhibitor Enzyme P29466 CASP1_HUMAN Details
T03 Peroxisome proliferator-activated receptor alpha PPARA agonist Nuclear hormone receptor Q07869 PPARA_HUMAN Details
T21 Diacylglycerol O-acyltransferase 2 DGAT2 inhibitor Enzyme Q96PD7 DGAT2_HUMAN Details

Diseases ID DO ID Disease Name Definition Class
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