Zenidolol

Details

Stereochemistry	RACEMIC
Molecular Formula	C17H27NO2
Molecular Weight	277.4018
Optical Activity	( + / - )
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)N[C@H](C)[C@@H](O)COC1=C2CCCC2=C(C)C=C1

InChI

InChIKey=VFIDUCMKNJIJTO-CJNGLKHVSA-N

InChI=1S/C17H27NO2/c1-11(2)18-13(4)16(19)10-20-17-9-8-12(3)14-6-5-7-15(14)17/h8-9,11,13,16,18-19H,5-7,10H2,1-4H3/t13-,16+/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15908513 | https://www.ncbi.nlm.nih.gov/pubmed/18652905 | https://www.ncbi.nlm.nih.gov/pubmed/2900871 | https://www.ncbi.nlm.nih.gov/pubmed/2570461 | https://www.ncbi.nlm.nih.gov/pubmed/19470879 | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1987085/ http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2125.1988.tb03326.x/pdfhttps://www.ncbi.nlm.nih.gov/pubmed/27602067
Curator's Comment: The description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/28064316 | https://www.ncbi.nlm.nih.gov/pubmed/26762097 | https://www.ncbi.nlm.nih.gov/pubmed/3320184 | https://www.ncbi.nlm.nih.gov/pubmed/2908820

ICI-118551 is a selective β2 adrenergic receptor antagonist, that was originally developed for the regulation of blood pressure. ICI-118551 crosses the blood-brain barrier and it was in phase I clinical trials for the treatment of chronic anxiety. Currently, ICI-118,551 has no known therapeutic use in humans although it has been used widely in research to understand the action of the β2 adrenergic receptor, as few other specific antagonists for this receptor are known.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Beta-2 adrenergic receptor 209 Target ID: CHEMBL210 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23614528	Antagonist 2849	1.2 nM [IC50]
Beta-1 adrenergic receptor 163 Target ID: CHEMBL213 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23614528	Antagonist 2849	240.0 nM [Kd]
Alpha-2a adrenergic receptor 70 Target ID: CHEMBL1867 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23582449	Antagonist 2849	0.5 nM [IC50]
Beta-2 adrenergic receptor 209 Target ID: P07550\|\|\|Q53GA6\|\|\|Q9UCZ3 Gene ID: 154.0 Gene Symbol: ADRB2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/6191142 \| https://www.ncbi.nlm.nih.gov/pubmed/8853440	Antagonist 2849	2.0 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Chronic anxiety 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3320184	Primary	Phase I 438	Unknown Approved Use Unknown
Essential tremor 6 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2894217	Primary	Not Provided 511	Unknown Approved Use Unknown
Hypertension 575 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2898256	Primary	Phase I 438	Unknown Approved Use Unknown
Pulmonary arterial hypertension 36 Sources: http://hyper.ahajournals.org/content/54/1/157	Primary	Preclinical	Unknown Approved Use Unknown
Elevated intraocular pressure 9 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6150744	Primary	Preclinical	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
50 mg 3 times / day multiple, oral Studied dose Dose: 50 mg, 3 times / day Route: oral Route: multiple Dose: 50 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2564208/	unhealthy Health Status: unhealthy Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2564208/	Other AEs: headache... Other AEs: headache (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/2564208/

AEs

AE	Significance	Dose	Population
headache	2 patients	50 mg 3 times / day multiple, oral Studied dose Dose: 50 mg, 3 times / day Route: oral Route: multiple Dose: 50 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2564208/	unhealthy Health Status: unhealthy Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2564208/

PubMed

Title	Date	PubMed
[Changes in the receptor activity of β2-adrenoreceptors of human T-lymphocytes under the effect of β2-agonists].	2015-10-21	28064316
beta(2)-adrenoceptor antagonist ICI 118,551 decreases pulmonary vascular tone in mice via a G(i/o) protein/nitric oxide-coupled pathway.	2009-07	19470879
A cell-based assay to assess the persistence of action of agonists acting at recombinant human beta(2) adrenoceptors.	2007-12-16	18652905
Functional characterization of the beta-adrenergic receptor subtypes expressed by CA1 pyramidal cells in the rat hippocampus.	2005-08	15908513
Nicotine-induced NO-mediated increase in cortical cerebral blood flow is blocked by beta2-adrenoceptor antagonists in the anesthetized rats.	2002-03-18	11958478
Beta-adrenoceptor subtypes and the opening of plasmalemmal K(+)-channels in trachealis muscle: electrophysiological and mechanical studies in guinea-pig tissue.	1993-08	8104643
Molecular characterization of the human beta 3-adrenergic receptor.	1989-09-08	2570461
Beta 1- and beta 2-adrenergic receptor-mediated adenylate cyclase stimulation in nonfailing and failing human ventricular myocardium.	1989-03	2564629
Human fat cell beta-adrenergic receptors: beta-agonist-dependent lipolytic responses and characterization of beta-adrenergic binding sites on human fat cell membranes with highly selective beta 1-antagonists.	1988-05	2900871
The pharmacology of a beta 2-selective adrenoceptor antagonist (ICI 118,551).	1983-05-01	6191142

Patents

Sample Use Guides

In Vivo Use Guide

ICI 118,551, 50 mg given thrice daily, in hypertensive patients known to respond to therapy with atenolol or propranolol.

Route of Administration: Oral

In Vitro Use Guide

In cultured rat inner medullary collecting duct (IMCD) cells expressing beta-adrenoceptor subtype(s) ICI-118551 inhibited adenosine 3',5'-cyclic monophosphate (cAMP) accumulation by 50% at 1.7 uM.

Name

Type

Language

Zenidolol

Official Name

English

(±)-ICI-118551

Preferred Name

English

REL-(2R,3S)-1-((2,3-DIHYDRO-7-METHYL-1H-INDEN-4-YL)OXY)-3-((1-METHYLETHYL)AMINO)-2-BUTANOL

Common Name

English

2-BUTANOL, 1-((2,3-DIHYDRO-7-METHYL-1H-INDEN-4-YL)OXY)-3-((1-METHYLETHYL)AMINO)-, (2R,3R)-REL-

Systematic Name

English

rac-(2R,3R)-1-[(7-methyl-2,3-dihydro-1H-inden-4- yl)oxy]-3-[(propan-2-yl)amino]butan-2-ol

Systematic Name

English

ICI-118,551

Code

English

zenidolol [INN]

Common Name

English

ICI-118551

Code

English

Code System Code Type Description

EPA CompTox

DTXSID701033231