General
Preferred name
ATENOLOL
Synonyms
ESATENOLOL ()
(±)-Atenolol ()
(RS)-Atenolol ()
Tenormin ()
Normiten ()
Blokium ()
Tenormin, Normiten, Blokium ()
Atenix-25 ()
Juvental ()
ICI-66082 ()
ICI 66082 ()
NSC-757832 ()
Atenix-50 ()
Prenormine ()
Antipressan ()
Tenormin L.S. ()
Betacard ()
Ibinolo ()
Tenormin 25 ()
Unibloc ()
Atenamin ()
Kentol ()
C07AB03 ()
Vasaten ()
Atenololum ()
Duraatenolol ()
Atenix-100 ()
Totamol ()
ICI 66,082 ()
Corotenol ()
Novaten ()
Myocord ()
Urosin ()
?(±)-Atenolol ()
(+)-Atenolol-d7 ()
P&D ID
PD001885
CAS
29122-68-7
60966-51-0
106020-65-9
1202864-50-3
Tags
natural product
drug
available
Approved by
FDA
First approval
1981
Drug Status
approved
Drug indication
Hypertension
Anti-Adrenergic (beta-receptor)
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
INDICATION
**Indicated** for:[label]; ; 1) Management of hypertension alone and in combination with other antihypertensives.; ; 2) Management of angina pectoris associated with coronary atherosclerosis.; ; 3) Management of acute myocardial infarction in hemodynamically stable patients with a heart rate greater than 50 beats per minutes and a systolic blood pressure above 100 mmHg.; ; **Off-label** uses include:; ; 1) Secondary prevention of myocardial infarction.[A178156]; ; 2) Management of heart failure.[A178153]; ; 3) Management of atrial fibrillation.[A178141]; ; 4) Management of supraventricular tachycardia.[A178162]; ; 5) Management of ventricular arrythmias such as congenital long-QT and arrhythmogenic right ventricular cardiomyopathy.[A178168]; ; 6) Management of symptomatic thyrotoxicosis in combination with [methimazole].[A178147]; ; 7) Prophylaxis of migraine headaches.[A178171]; ; 8) Management of alcohol withdrawal.[A178174,A178177]
MOA
Atenolol is a cardioselective beta-blocker, called such because it selectively binds to the β1-adrenergic receptor as an antagonist up to a reported 26 fold more than β2 receptors.[A178372] Selective activity at the β1 receptor produces cardioselectivity due to the higher population of this receptor in cardiac tissue. Some binding to β2 and possibly β3 receptors can still occur at therapeutic dosages but the effects mediated by antagonizing these are significantly reduced from those of non-selective agents. β1 and β2 receptors are Gs coupled therefore antagonism of their activation reduces activity of adenylyl cyclase and its downstream signalling via cyclic adenosime monophosphate and protein kinase A (PKA). ; ; In cardiomyocytes PKA is thought to mediate activation of L-type calcium channels and ryanodine receptors through their phosphorylation.[A178396] L-type calcium channels can then provide an initial rise in intracellular calcium and trigger the ryanodine receptors to release calcium stored in the sarcoplasmic reticulum (SR) and increased contractility. PKA also plays a role in the cessation of contraction by phosphorylating phospholamban which in turn increases the affinity of SR Ca2+ ATPase to increase reuptake of calcium into the SR. It also phophorylates troponin I to reduce affinity of the protein for calcium. Both of these events lead to a reduction in contraction which, when coupled with the initial increase in contraction, allows for faster cycling and consequently higher heart rate with increased contractility. L-type calcium channels are also a major contributor to cardiac depolarization and their activation can increase frequency of action potentials and possibly the incidence of ectopic potentials.[A178405] ; ; Similar inihibitory events occur in the bronchial smooth muscle to mediate relaxation including phosphorylation of myosin light-chain kinase, reducing its affinity for calcium.[A178408] PKA also inhibits the excitatory Gq coupled pathway by phosphorylating the inositol trisphosphate receptor and phospholipase C resulting in inhibition of intracellular calcium release. Antagonism of this activity by beta-blocker agents like atenolol can thus cause increased bronchoconstriction.;
DESCRIPTION
Atenolol is a selective β1-adrenoceptor antagonist (β blocker), developed as a replacement for .
(GtoPdb)
METABOLISM
Minimal metabolism in the liver.[label] The sole non-conjugated metabolite is the product of a hydroxylation reaction at the carbon between the amide and benzene groups.[A178204] The only other metabolite to be confirmed is a glucuronide conjugate. These metabolites make up 5-8% and 2% of the renally excreted dose with 87-90% appearing as unchanged drug. The hydroxylated metabolite is exerts 1/10th the beta-blocking activity of atenolol.
TOXICITY
**LD50 Values**; ; Mouse: 2 g/kg (Oral), 57 mg/kg (IV), 134 mg/kg (IP), 400 mg/kg (SC)[L6316]; ; Rat: 2 g/kg (Oral), 77 mg/kg (IV), 600 mg/kg (SC)[L6316]; ; Rabbit: 50 mg/kg (IV)[L6316]; ; **Carcinogenicity & Mutagenicity**; ; Studies in rats and mice at doses of 300 mg/kg/day, equivalent to 150 times maximum recommended human dose, for durations of 18 and 24 months showed no carcinogenicity.[label] One study in rats at doses of 500-1500 mg/kg/day, 250-750 times maximum human dose, resulted in increases benign adrenal medullary tumors in both sexes and increase mammary fibroadenomas in females.; ; Atenolol showed no mutagenicity in the Ames test using _S. typhinarium_, dominant lethal test in mice, or _in vivo_ cytogenetics test in chinese hamster ovary cells.[label]; ; **Reproductive Toxicity**; ; No adverse effects on fertility were observed in either male or female mice after receiving doses of 200 mg/kg/day, equivalent to 200 times the maximum human dose. In humans, atenolol is known to cross the placenta and fetuses exposed to the drug have been reported to be smaller than expected considering gestational age. Embryo-fetal resorption has been observed in rats at doses of 50mg/kg/day, 50 times the max human dose, but not in rabbits at doses of 25mg/kg/day.[label]; ; **Lactation**; ; Atenolol appears in breast milk at a ratio of 1.5-6.8 to plasma concentrations.[label] It has been estimated that infant exposure occurs at 5.7-19.2% maternal weight-adjusted dosage.[L6313] Effects in infants include bradycardia, hypothermia, and lethargy.
ABSORPTION
Approximately 50% of an oral dose is absorbed from the gastrointestinal tract, with the remainder being excreted unchanged in the feces.[label] Administering atenolol with food can decrease the AUC by about 20%.[A178180] While atenolol can cross the blood-brain barrier, it does so slowly and to a small extent.
ROE
85% is eliminated by the kidneys following IV administration with 10% appearing in the feces.[label,A178180]
HALF-LIFE
6-7 hrs.[label]
DESCRIPTION
Selective beta1 adrenoceptor antagonist;;antihypertensive; antianginal; antiarrhythmic
(LOPAC library)
DESCRIPTION
β1 antagonist
(Tocriscreen Total)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Compound Sets
32
CeMM library of unique drugs (CLOUD)
ChEMBL Approved Drugs
ChEMBL Drugs
Concise Guide to Pharmacology 2017/18
Concise Guide to Pharmacology 2019/20
Concise Guide to Pharmacology 2021/22
Concise Guide to Pharmacology 2023/24
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
DrugMatrix
Enamine BioReference Compounds
EU-OPENSCREEN Bioactive Compound Library
Guide to Pharmacology
Ki Database
LOPAC library
LSP-MoA library (Laboratory of Systems Pharmacology)
Mcule NIBR MoA Box Subset
MedChem Express Bioactive Compound Library
NCATS Inxight Approved Drugs
NIH Clinical Collections (NCC)
Novartis Chemogenetic Library (NIBR MoA Box)
NPC Screening Collection
ReFrame library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
The Spectrum Collection
Tocriscreen Total
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
42
Molecular Weight
266.16
Hydrogen Bond Acceptors
4
Hydrogen Bond Donors
3
Rotatable Bonds
8
Ring Count
1
Aromatic Ring Count
1
cLogP
0.45
TPSA
84.58
Fraction CSP3
0.5
Chiral centers
1.0
Largest ring
6.0
QED
0.64
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Selectivity
beta1
MOA
Adrenergic Receptor antagonist
beta1-Adrenoceptor Antagonists
Target
Beta-1 adrenergic receptor
??1-adrenergic receptor
??2-adrenergic receptor
¦Â1-adrenergic receptor
¦Â2-adrenergic receptor
?? receptor,?? receptor
Adrenergic Receptor
Pathway
GPCR/G protein
Neuronal Signaling
Member status
member
Therapeutic Class
Antihypertensive Agents
Source data
