PRONETALOL

Details

Stereochemistry	RACEMIC
Molecular Formula	C15H19NO
Molecular Weight	229.3175
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)NCC(O)C1=CC=C2C=CC=CC2=C1

InChI

InChIKey=HRSANNODOVBCST-UHFFFAOYSA-N

InChI=1S/C15H19NO/c1-11(2)16-10-15(17)14-8-7-12-5-3-4-6-13(12)9-14/h3-9,11,15-17H,10H2,1-2H3

HIDE SMILES / InChI

Molecular Formula	C15H19NO
Molecular Weight	229.3175
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: http://www.sciencedirect.com/science/article/pii/B9780080552323624742 | https://www.ncbi.nlm.nih.gov/pubmed/20590649 | https://www.ncbi.nlm.nih.gov/pubmed/16502872 | https://www.ncbi.nlm.nih.gov/pubmed/9456487

Pronetalol (Pronethalol) is a nonselective beta-adrenoceptor antagonist that is structurally related to propranolol. Pronethalol displays a ∼125–150-fold lower affinity (140–830 nM) for beta-adrenoceptors than propranolol (1.1–5.7 nM). Pronethalol was the first beta-adrenoceptor antagonist used for the treatment of coronary heart disease and cardiac arrhythmias. Pronethalol is a cationic-amphiphilic agent that exhibits membrane-stabilizing effects that are unrelated to beta-adrenoceptor blockade. Pronetalol itself never came into widespread clinical use; it was found to produce thymic tumors in mice, and was discarded in favor of a similar, safer compound, ICI 45,520.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Adrenergic receptor beta 87 Target ID: CHEMBL2094118 Sources: http://www.sciencedirect.com/science/article/pii/B9780080552323624742 \| https://www.ncbi.nlm.nih.gov/pubmed/2894664 \| https://www.ncbi.nlm.nih.gov/pubmed/18157	Antagonist 2778		140.0 nM [Kd]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cardiac arrhythmia 19 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2894664 https://www.ncbi.nlm.nih.gov/pubmed/14110746 https://www.ncbi.nlm.nih.gov/pubmed/9628	Primary		Withdrawn	Unknown Approved Use Unknown
Angina pectoris 106 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14297521 https://www.ncbi.nlm.nih.gov/pubmed/14056892	Primary		Withdrawn	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Blockade of epinephrine- and ouabain-induced cardiac arrhythmias in the dog heart-lung preparation.	1966 May	4380269
The mechanics of left ventricular contraction in acute experimental cardiac failure.	1967 Mar	4381563
Tremorine-oxotremorine-induced tremor, hypothermia and analgesia, and physostigmine toxicity, in mice after pretreatment with beta-adrenoceptor antagonists.	1976 Apr	6716
Determination of propranolol concentration in small volume of rat plasma by HPLC with fluorometric detection.	2001 Dec	11748690
Non-aqueous capillary electrophoretic separation of enantiomeric amines with (-)-2,3:4,6-di-O-isopropylidene-2-keto-L-gulonic acid as chiral counter ion.	2001 Jul 13	11486876
Development of a chiral non-aqueous capillary electrophoretic system using the partial filling technique with UV and mass spectrometric detection.	2003 Jan 31	12585332
The role of beta-blockers as a cornerstone of cardiovascular therapy.	2005 Dec	16373194
The use of metoprolol CR/XL in the treatment of patients with diabetes and chronic heart failure.	2006	17319457
Putting theory into practice: James Black, receptor theory and the development of the beta-blockers at ICI, 1958-1978.	2006 Jan	16502872
Multiple GPCR conformations and signalling pathways: implications for antagonist affinity estimates.	2007 Aug	17629959
A case of serendipity*.	2008 Jun	18368517
Antagonist affinity measurements at the Gi-coupled human histamine H3 receptor expressed in CHO cells.	2008 Jun 6	18538007
Quantitative analysis of propranolol hydrochloride by high performance thin layer chromatography.	2008 May-Jun	20046758
Analytical and experimental pharmacology, challenges ahead.	2010	21734890
Comparison of some properties of pronethalol and propranolol. 1965.	2010 Jul	20590649

Patents

Sample Use Guides

In Vivo Use Guide

Guinea-pigs: In one series of experiments, 5 mg/kg of pronethalol was injected, and in another 15 mg/kg. Pronethalol (5 mg/kg), increased the dose of ouabain required to produce extrasystoles, completely prevented fibrillation, and significantly raised the lethal dose of ouabain. When fibrillation had already been produced by ouabain, pronethalol (3 to 4 mg) administered slowly restored a regular rhythm, but rapid injection sometimes produced cardiac arrest. As much as 20 to 25 mg/kg of pronethalol could be given to animals deeply anaesthetized with urethane or pentobarbitone, but with light chloroform or ether anaesthesia, 5 mg/kg of pronethalol caused a large fall in blood pressure and complete heart-block.

Route of Administration: Intravenous

In Vitro Use Guide

Pronethalol (6.8 x 10(-5)M) reversed the alpha-receptor blockade by dibenamine, ergotamine and phentolamine of responses to adrenaline, noradrenaline and phenylephrine in guinea-pig seminal vesicle.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 17:50:09 GMT 2023` Edited by `admin` on `Sat Dec 16 17:50:09 GMT 2023`
Record UNII	XBP4RT1IMQ
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

PRONETALOL

Official Name

English

AY-6204 FREE BASE

Code

English

Pronetalol [WHO-DD]

Common Name

English

NETHALIDE

Common Name

English

2-ISOPROPYLAMINO-1-(NAPHTH-2-YL)ETHANOL

Systematic Name

English

NETH

Common Name

English

COMPOUND 38174

Code

English

DL-PRONETHALOL

Common Name

English

GNF-PF-2670

Code

English

ICI 38174 FREE BASE

Code

English

PRONETHALOL [MI]

Common Name

English

PRONETHALOL

Common Name

English

AY-6204 HCL

Code

English

pronetalol [INN]

Common Name

English

NAPHTHYLISOPROTERENOL

Common Name

English

ICI-38174 FREE BASE

Code

English

INETOL

Brand Name

English

AY 6204 FREE BASE

Code

English

2-NAPHTHALENEMETHANOL, .ALPHA.-(((1-METHYLETHYL)AMINO)METHYL)-

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29576