XAMOTEROL

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 Search

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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2862938 | https://www.ncbi.nlm.nih.gov/pubmed/6128041
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

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Beta-1 adrenergic receptor 158 Target ID: CHEMBL213 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6128041 \| https://www.ncbi.nlm.nih.gov/pubmed/2862938	Partial Agonist 290

Conditions

Condition	Modality	Targets	Highest Phase	Product
Heart failure 103 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1967561 https://www.ncbi.nlm.nih.gov/pubmed/1971596 https://www.ncbi.nlm.nih.gov/pubmed/8465800	Primary		Approved 8429	CORWIN Approved Use Xamoterol (Fumarate) is primarily indicated in conditions like Heart failure.

PubMed

Title	Date	PubMed
Comparative analysis of beta-1 adrenoceptor agonist and antagonist potency and selectivity of cicloprolol, xamoterol and pindolol.	1987 Sep	2888869
Xamoterol improves the control of chronic atrial fibrillation in elderly patients.	1995 Jul	7484490
Ketotifen and cardiovascular effects of xamoterol following single and chronic dosing in healthy volunteers.	1999 Jan	10073741
Binding pockets of the beta(1)- and beta(2)-adrenergic receptors for subtype-selective agonists.	1999 Nov	10531390
Cardioselective beta-blocker use in patients with reversible airway disease.	2001	11406056
Beta2-adrenoceptor-mediated prejunctional facilitation and postjunctional inhibition of sympathetic neuroeffector transmission in the guinea pig vas deferens.	2001 Aug	11454924
Constitutive activity of the human beta(1)-adrenergic receptor in beta(1)-receptor transgenic mice.	2001 Oct	11562432
beta-Adrenergic receptors, transgenic mice, and pharmacological model systems.	2001 Oct	11562422
Neurohormonal activation in heart failure after acute myocardial infarction treated with beta-receptor antagonists.	2002 Jan	11812667
Adenylate cyclase activity in postmortem brain of suicide subjects: reduced response to beta-adrenergic stimulation.	2003 Dec 15	14675811
Beta 3-adrenergic receptors regulate retinal endothelial cell migration and proliferation.	2003 Jun 6	12670949
Heme oxygenase-1 gene expression in pericentral hepatocytes through beta1-adrenoceptor stimulation.	2004 Apr	15179140
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	15276075
Beta1-adrenergic receptors maintain fetal heart rate and survival.	2006	16210849
Are we misunderstanding beta-blockers.	2007 Aug 9	17433471
beta(2) and beta(3)-adrenoceptor inhibition of alpha(1)-adrenoceptor-stimulated Ca(2+) elevation in human cultured prostatic stromal cells.	2007 Sep 10	17617401
Carvedilol in the treatment of elderly patients with chronic heart failure.	2008	18488879
The adrenergic receptor subtypes present in frog (Rana esculenta) skin.	2008 Aug	18544474
Restoration of norepinephrine-modulated contextual memory in a mouse model of Down syndrome.	2009 Nov 18	20368182
Beta-blockers and heart failure.	2010 Mar-Apr	21180298

Patents

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 `Fri Dec 15 16:07:52 GMT 2023` Edited by `admin` on `Fri Dec 15 16:07:52 GMT 2023`
Record UNII	7HE0JQL703
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

XAMOTEROL

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