PRONETHALOL HYDROCHLORIDE

Withdrawn

Details

Stereochemistry	RACEMIC
Molecular Formula	C15H19NO.ClH
Molecular Weight	265.778
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

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

InChI

InChIKey=QONLGXRPRAIDGI-UHFFFAOYSA-N

InChI=1S/C15H19NO.ClH/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;1H

HIDE SMILES / InChI

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C15H19NO
Molecular Weight	229.3175
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

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

Description

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 89	Antagonist 2,849		140.0 nM [Kd]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cardiac arrhythmia 19	Primary		Withdrawn	Unknown
Angina pectoris 110	Primary		Withdrawn	Unknown

PubMed

Show entries

Title	Date	PubMed
The use of metoprolol CR/XL in the treatment of patients with diabetes and chronic heart failure.	2006	17319457
Multiple GPCR conformations and signalling pathways: implications for antagonist affinity estimates.	2007 Aug	17629959
Analytical and experimental pharmacology, challenges ahead.	2010	21734890
Comparison of some properties of pronethalol and propranolol. 1965.	2010 Jul	20590649

Showing 1 to 4 of 4 entries

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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.