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Details

Stereochemistry RACEMIC
Molecular Formula 2C16H25N3O5.C4H4O4
Molecular Weight 794.8458
Optical Activity ( + / - )
Defined Stereocenters 0 / 2
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of XAMOTEROL FUMARATE

SMILES

OC(=O)\C=C\C(O)=O.OC(CNCCNC(=O)N1CCOCC1)COC2=CC=C(O)C=C2.OC(CNCCNC(=O)N3CCOCC3)COC4=CC=C(O)C=C4

InChI

InChIKey=QEDVGROSOZBGOZ-WXXKFALUSA-N
InChI=1S/2C16H25N3O5.C4H4O4/c2*20-13-1-3-15(4-2-13)24-12-14(21)11-17-5-6-18-16(22)19-7-9-23-10-8-19;5-3(6)1-2-4(7)8/h2*1-4,14,17,20-21H,5-12H2,(H,18,22);1-2H,(H,5,6)(H,7,8)/b;;2-1+

HIDE SMILES / InChI

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/1967561 | https://www.ncbi.nlm.nih.gov/pubmed/1971596 | https://www.ncbi.nlm.nih.gov/pubmed/8465800

Xamoterol (ICI 118,587) is a partial agonist of beta1-adrenoceptors. Xamoterol acts on the cardiac beta 1-adrenergic receptor, modifies the response of the heart to variations in sympathetic activity. At rest, it produces modest improvements in cardiac contractility, relaxation, and filling without increase in myocardial oxygen demand. The improvements are maintained during exercise although the attendant tachycardia is attenuated. The beneficial effects of xamoterol on both systolic and diastolic function suggested that it would be effective in patients with mild-to-moderate heart failure, and this was demonstrated in small placebo-controlled studies where effort tolerance and symptoms were improved. Xamoterol produced improvements in exercise capacity, clinical signs, symptoms and quality of life with a low incidence of adverse experiences. Xamoterol is effective as monotherapy in heart failure.

CNS Activity

Originator

Sources: BARLOW, J.J., MAIN, B.G., NUTTALL, A., MOORS, J. & SNOW, H.M. (1979). The cardiovascular activity of ICI118,587, a novel beta-adrenoceptor partial agonist. Br. J. Pharmac., 67, 412P.
Curator's Comment: http://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.1979.tb08695.x/epdf

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
CORWIN

Approved Use

Xamoterol (Fumarate) is primarily indicated in conditions like Heart failure.
PubMed

PubMed

TitleDatePubMed
Comparative analysis of beta-1 adrenoceptor agonist and antagonist potency and selectivity of cicloprolol, xamoterol and pindolol.
1987 Sep
Contrasting effects of single doses of pindolol and xamoterol on left ventricular diastolic function.
1989
Xamoterol improves the control of chronic atrial fibrillation in elderly patients.
1995 Jul
Binding pockets of the beta(1)- and beta(2)-adrenergic receptors for subtype-selective agonists.
1999 Nov
Cardioselective beta-blocker use in patients with reversible airway disease.
2001
The underreporting of results and possible mechanisms of 'negative' drug trials in patients with chronic heart failure.
2001 Aug
Beta2-adrenoceptor-mediated prejunctional facilitation and postjunctional inhibition of sympathetic neuroeffector transmission in the guinea pig vas deferens.
2001 Aug
Constitutive activity of the human beta(1)-adrenergic receptor in beta(1)-receptor transgenic mice.
2001 Oct
beta-Adrenergic receptors, transgenic mice, and pharmacological model systems.
2001 Oct
Cardioselective beta-blockers for reversible airway disease.
2002
Rapid component I(Kr) of the guinea-pig cardiac delayed rectifier K(+) current is inhibited by beta(1)-adrenoreceptor activation, via cAMP/protein kinase A-dependent pathways.
2002 Feb 1
Characterization of beta-adrenoceptor subtype in bladder smooth muscle in cynomolgus monkey.
2002 Jan
Neurohormonal activation in heart failure after acute myocardial infarction treated with beta-receptor antagonists.
2002 Jan
Bucindolol displays intrinsic sympathomimetic activity in human myocardium.
2002 May 21
Adenylate cyclase activity in postmortem brain of suicide subjects: reduced response to beta-adrenergic stimulation.
2003 Dec 15
Pharmacological characterization of putative beta1-beta2-adrenergic receptor heterodimers.
2003 Feb
Partial agonist activity of bucindolol is dependent on the activation state of the human beta1-adrenergic receptor.
2003 Jul 22
Beta 3-adrenergic receptors regulate retinal endothelial cell migration and proliferation.
2003 Jun 6
Functional and molecular characterization of beta-adrenoceptors in the internal anal sphincter.
2003 May
Heme oxygenase-1 gene expression in pericentral hepatocytes through beta1-adrenoceptor stimulation.
2004 Apr
Adrenergic regulation of vascular smooth muscle tone in calf digital artery.
2004 Aug
Agonist binding and activation of the rat beta(1)-adrenergic receptor: role of Trp(134(3.28)), Ser(190(4.57)) and Tyr(356(7.43)).
2004 Aug 15
Role of adenylate and guanylate cyclases in beta1-, beta2-, and beta3-adrenoceptor-mediated relaxation of internal anal sphincter smooth muscle.
2004 Mar
Dobutamine inhibits phorbol-myristate-acetate-induced activation of nuclear factor-kappaB in human T lymphocytes in vitro.
2004 Nov
Effect of overexpressed adenylyl cyclase VI on beta 1- and beta 2-adrenoceptor responses in adult rat ventricular myocytes.
2004 Oct
Glucocorticoid effects on memory retrieval require concurrent noradrenergic activity in the hippocampus and basolateral amygdala.
2004 Sep 15
A clinical, physiology and pharmacology evaluation of orthostatic hypotension in the elderly.
2005
In vitro evidence that carteolol is a nonconventional partial agonist of guinea pig cardiac beta1-adrenoceptors: a comparison with xamoterol.
2005 Dec
Sulfation in dog.
2005 Jun
Site of action of beta-ligands at the human beta1-adrenoceptor.
2005 Jun
Beta1-adrenergic receptors maintain fetal heart rate and survival.
2006
Functional beta-adrenergic receptor signalling on nuclear membranes in adult rat and mouse ventricular cardiomyocytes.
2006 Jul 1
NNK activates ERK1/2 and CREB/ATF-1 via beta-1-AR and EGFR signaling in human lung adenocarcinoma and small airway epithelial cells.
2006 Oct 1
Carvedilol in the treatment of chronic heart failure: lessons from the Carvedilol Or Metoprolol European Trial.
2007
Are we misunderstanding beta-blockers.
2007 Aug 9
Advanced-glycation end products (AGEs) derived from glycated albumin suppress early beta1-adrenergic preconditioning.
2007 Feb
Sympathetic neurotransmission modulates expression of inflammatory markers in the rat retina.
2007 Jan
beta(2) and beta(3)-adrenoceptor inhibition of alpha(1)-adrenoceptor-stimulated Ca(2+) elevation in human cultured prostatic stromal cells.
2007 Sep 10
Understanding cardiac output.
2008
Carvedilol in the treatment of elderly patients with chronic heart failure.
2008
The adrenergic receptor subtypes present in frog (Rana esculenta) skin.
2008 Aug
Beta-adrenergic receptor stimulation modulates iNOS protein levels through p38 and ERK1/2 signaling in human retinal endothelial cells.
2008 Jul
Effect of inhibition of extracellular signal-regulated kinase on relaxations to beta-adrenoceptor agonists in porcine isolated blood vessels.
2009 Dec
Four close bupranolol analogues are antagonists at the low-affinity state of beta1-adrenoceptors.
2009 Mar
Restoration of norepinephrine-modulated contextual memory in a mouse model of Down syndrome.
2009 Nov 18
Maintenance of beta-adrenergic receptor signaling can reduce Fas signaling in human retinal endothelial cells.
2009 Oct
Chronic treatment with agonists of beta(2)-adrenergic receptors in neuropathic pain.
2010 Jan
The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation.
2010 Jun
Beta-blockers and heart failure.
2010 Mar-Apr
A full pharmacological analysis of the three turkey β-adrenoceptors and comparison with the human β-adrenoceptors.
2010 Nov 30
Patents

Patents

Sample Use Guides

Xamoterol at 200 mg and 400 mg orally once daily had no effect on the mean resting heart rate but there was a small (5.7 beats min-1) but significant reduction in resting heart rate on 600 mg at 2-2.5 h after dosing. All three doses of xamoterol significantly reduced the maximum exercise heart rate at 2-2.5 h after dosing. Xamoterol at all three doses significantly increased exercise duration at 2-2.5 h after dosing but not at 24 h.
Route of Administration: Oral
human microvascular retinal endothelial cells (HMREC) cultured in high (25 mM) and low glucose (5 mM) conditions were serum starved for 18-24 h, followed by treatment with a beta-1-adrenergic receptor agonist, xamoterol (10 microM), for 15, 30, and 45 min.
Name Type Language
XAMOTEROL FUMARATE
MART.   USAN   WHO-DD  
USAN  
Official Name English
XAMOTEROL FUMARATE [USAN]
Common Name English
ICI-118,587 HEMIFUMARATE
Common Name English
ICI-118587 HEMIFUMARATE
Common Name English
Xamoterol fumarate [WHO-DD]
Common Name English
4-MORPHINOLINECARBOXAMIDE, N-*(2-((2-HYDROXY-3-(4-HYDROXYPHENOXY)PROPYL)AMINO)ETHYL)-, (±)-, (E)-2-BUTENEDIOATE (2:1) (SALT)
Common Name English
XAMOTEROL HEMIFUMARATE [MI]
Common Name English
XAMOTEROL FUMARATE [MART.]
Common Name English
(±)-N-(2-((2-HYDROXY-3-(P-HYDROXYPHENOXY)PROPYL)AMINO)ETHYL)-4-MORPHOLINECARBOXAMIDE FUMARATE (2:1) (SALT)
Common Name English
XAMOTEROL FUMARATE [JAN]
Common Name English
ICI 118,587
Code English
XAMOTEROL HEMIFUMARATE
MI  
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C78322
Created by admin on Fri Dec 15 18:51:55 GMT 2023 , Edited by admin on Fri Dec 15 18:51:55 GMT 2023
NCI_THESAURUS C48149
Created by admin on Fri Dec 15 18:51:55 GMT 2023 , Edited by admin on Fri Dec 15 18:51:55 GMT 2023
Code System Code Type Description
USAN
BB-31
Created by admin on Fri Dec 15 18:51:55 GMT 2023 , Edited by admin on Fri Dec 15 18:51:55 GMT 2023
PRIMARY
PUBCHEM
6440459
Created by admin on Fri Dec 15 18:51:55 GMT 2023 , Edited by admin on Fri Dec 15 18:51:55 GMT 2023
PRIMARY
CAS
90730-93-1
Created by admin on Fri Dec 15 18:51:55 GMT 2023 , Edited by admin on Fri Dec 15 18:51:55 GMT 2023
SUPERSEDED
NCI_THESAURUS
C152925
Created by admin on Fri Dec 15 18:51:55 GMT 2023 , Edited by admin on Fri Dec 15 18:51:55 GMT 2023
PRIMARY
MERCK INDEX
m11523
Created by admin on Fri Dec 15 18:51:55 GMT 2023 , Edited by admin on Fri Dec 15 18:51:55 GMT 2023
PRIMARY Merck Index
CAS
73210-73-8
Created by admin on Fri Dec 15 18:51:55 GMT 2023 , Edited by admin on Fri Dec 15 18:51:55 GMT 2023
PRIMARY
EVMPD
SUB05144MIG
Created by admin on Fri Dec 15 18:51:55 GMT 2023 , Edited by admin on Fri Dec 15 18:51:55 GMT 2023
PRIMARY
DRUG BANK
DBSALT002913
Created by admin on Fri Dec 15 18:51:55 GMT 2023 , Edited by admin on Fri Dec 15 18:51:55 GMT 2023
PRIMARY
FDA UNII
N87007N668
Created by admin on Fri Dec 15 18:51:55 GMT 2023 , Edited by admin on Fri Dec 15 18:51:55 GMT 2023
PRIMARY
RXCUI
82133
Created by admin on Fri Dec 15 18:51:55 GMT 2023 , Edited by admin on Fri Dec 15 18:51:55 GMT 2023
PRIMARY RxNorm
ChEMBL
CHEMBL75753
Created by admin on Fri Dec 15 18:51:55 GMT 2023 , Edited by admin on Fri Dec 15 18:51:55 GMT 2023
PRIMARY
SMS_ID
100000087903
Created by admin on Fri Dec 15 18:51:55 GMT 2023 , Edited by admin on Fri Dec 15 18:51:55 GMT 2023
PRIMARY
ECHA (EC/EINECS)
277-319-9
Created by admin on Fri Dec 15 18:51:55 GMT 2023 , Edited by admin on Fri Dec 15 18:51:55 GMT 2023
PRIMARY