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Details

Stereochemistry RACEMIC
Molecular Formula C16H25N3O5
Molecular Weight 339.3868
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of XAMOTEROL

SMILES

OC(CNCCNC(=O)N1CCOCC1)COC2=CC=C(O)C=C2

InChI

InChIKey=DXPOSRCHIDYWHW-UHFFFAOYSA-N
InChI=1S/C16H25N3O5/c20-13-1-3-15(4-2-13)24-12-14(21)11-17-5-6-18-16(22)19-7-9-23-10-8-19/h1-4,14,17,20-21H,5-12H2,(H,18,22)

HIDE SMILES / InChI
Molecular Formula C16H25N3O5
Molecular Weight 339.3868
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

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

Imperial Chemical Industries
59
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

Unknown
134361
Targets

Targets

Primary TargetPharmacologyConditionPotency
Partial Agonist
288
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8360
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
Constitutive activity of the human beta(1)-adrenergic receptor in beta(1)-receptor transgenic mice.
2001 Oct
Characterization of beta-adrenoceptor subtype in bladder smooth muscle in cynomolgus monkey.
2002 Jan
Functional and molecular characterization of beta-adrenoceptors in the internal anal sphincter.
2003 May
Effect of overexpressed adenylyl cyclase VI on beta 1- and beta 2-adrenoceptor responses in adult rat ventricular myocytes.
2004 Oct
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
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
Are we misunderstanding beta-blockers.
2007 Aug 9
Sympathetic neurotransmission modulates expression of inflammatory markers in the rat retina.
2007 Jan
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
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
Beta-blockers and heart failure.
2010 Mar-Apr
Patents

Patents

US4143140
2

Sample Use Guides

In Vivo Use Guide
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
In Vitro Use Guide
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.
Substance Class Chemical
Created
by admin
on Wed Jul 05 23:35:35 UTC 2023
Edited
by admin
on Wed Jul 05 23:35:35 UTC 2023
Record UNII
7HE0JQL703
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
XAMOTEROL
INN   MI   USAN   WHO-DD  
INN   USAN  
Official Name English
4-MORPHOLINECARBOXAMIDE, N-(2-((2-HYDROXY-3-(4-HYDROXYPHENOXY)PROPYL)AMINO)ETHYL)-, (±)-
Systematic Name English
XAMOTEROL [USAN]
Common Name English
ICI-118587
Code English
XAMOTEROL [MI]
Common Name English
4-MORPHOLINECARBOXAMIDE, N-(2-((2-HYDROXY-3-(4-HYDROXYPHENOXY)PROPYL)AMINO)ETHYL)-, (±)-
Common Name English
(±)-N-(2-((2-HYDROXY-3-(P-HYDROXYPHENOXY)PROPYL)AMINO)ETHYL)-4-MORPHOLINECARBOXAMIDE
Common Name English
xamoterol [INN]
Common Name English
Xamoterol [WHO-DD]
Common Name English
ICI-118,587
Code English
Classification Tree Code System Code
NCI_THESAURUS C48149
Created by admin on Wed Jul 05 23:35:35 UTC 2023 , Edited by admin on Wed Jul 05 23:35:35 UTC 2023
WHO-VATC QC01CX07
Created by admin on Wed Jul 05 23:35:35 UTC 2023 , Edited by admin on Wed Jul 05 23:35:35 UTC 2023
WHO-ATC C01CX07
Created by admin on Wed Jul 05 23:35:35 UTC 2023 , Edited by admin on Wed Jul 05 23:35:35 UTC 2023
Code System Code Type Description
WIKIPEDIA
XAMOTEROL
Created by admin on Wed Jul 05 23:35:35 UTC 2023 , Edited by admin on Wed Jul 05 23:35:35 UTC 2023
PRIMARY
PUBCHEM
155774
Created by admin on Wed Jul 05 23:35:35 UTC 2023 , Edited by admin on Wed Jul 05 23:35:35 UTC 2023
PRIMARY
USAN
U-92
Created by admin on Wed Jul 05 23:35:35 UTC 2023 , Edited by admin on Wed Jul 05 23:35:35 UTC 2023
PRIMARY
EPA CompTox
DTXSID8045222
Created by admin on Wed Jul 05 23:35:35 UTC 2023 , Edited by admin on Wed Jul 05 23:35:35 UTC 2023
PRIMARY
MESH
D017307
Created by admin on Wed Jul 05 23:35:35 UTC 2023 , Edited by admin on Wed Jul 05 23:35:35 UTC 2023
PRIMARY
DRUG CENTRAL
2848
Created by admin on Wed Jul 05 23:35:35 UTC 2023 , Edited by admin on Wed Jul 05 23:35:35 UTC 2023
PRIMARY
FDA UNII
7HE0JQL703
Created by admin on Wed Jul 05 23:35:35 UTC 2023 , Edited by admin on Wed Jul 05 23:35:35 UTC 2023
PRIMARY
CAS
81801-12-9
Created by admin on Wed Jul 05 23:35:35 UTC 2023 , Edited by admin on Wed Jul 05 23:35:35 UTC 2023
PRIMARY
ChEMBL
CHEMBL75753
Created by admin on Wed Jul 05 23:35:35 UTC 2023 , Edited by admin on Wed Jul 05 23:35:35 UTC 2023
PRIMARY
SMS_ID
100000079329
Created by admin on Wed Jul 05 23:35:35 UTC 2023 , Edited by admin on Wed Jul 05 23:35:35 UTC 2023
PRIMARY
MERCK INDEX
M11523
Created by admin on Wed Jul 05 23:35:35 UTC 2023 , Edited by admin on Wed Jul 05 23:35:35 UTC 2023
PRIMARY Merck Index
NCI_THESAURUS
C81344
Created by admin on Wed Jul 05 23:35:35 UTC 2023 , Edited by admin on Wed Jul 05 23:35:35 UTC 2023
PRIMARY
INN
5271
Created by admin on Wed Jul 05 23:35:35 UTC 2023 , Edited by admin on Wed Jul 05 23:35:35 UTC 2023
PRIMARY
EVMPD
SUB00092MIG
Created by admin on Wed Jul 05 23:35:35 UTC 2023 , Edited by admin on Wed Jul 05 23:35:35 UTC 2023
PRIMARY
DRUG BANK
DB13781
Created by admin on Wed Jul 05 23:35:35 UTC 2023 , Edited by admin on Wed Jul 05 23:35:35 UTC 2023
PRIMARY
RXCUI
39801
Created by admin on Wed Jul 05 23:35:35 UTC 2023 , Edited by admin on Wed Jul 05 23:35:35 UTC 2023
PRIMARY RxNorm
Related Record Type Details
Structure of XAMOTEROL FUMARATE
SALT/SOLVATE -> PARENT
Structure of XAMOTEROL, (R)-
ENANTIOMER -> RACEMATE
Structure of XAMOTEROL, (S)-
ENANTIOMER -> RACEMATE
BETA-1 ADRENERGIC RECEPTOR
TARGET -> AGONIST
SHORT-ACTING
Related Record Type Details
Structure of XAMOTEROL
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