Propranolol

Structural formula
	( R ) -propranolol (top) and ( S ) -propranolol (bottom), 1: 1 stereoisomeric mixture
General
Non-proprietary name	Propranolol
other names	( RS ) -1- (Isopropylamino) -3- (naphthalen-1-yloxy) propan-2-ol ( IUPAC ); rac -1- (isopropylamino) -3- (naphthalen-1-yloxy) propan-2-ol; (±) -1- (Isopropylamino) -3- (naphthalen-1-yloxy) propan-2-ol; DL -1- (isopropylamino) -3- (naphthalen-1-yloxy) -2-propanol;
Molecular formula	C 16 H 21 NO 2
Brief description	white solid (hydrochloride)
External identifiers / databases
EC number	208-378-0
ECHA InfoCard	100.007.618
PubChem	4946
ChemSpider	4777
DrugBank	DB00571
Wikidata	Q423364
Drug information
ATC code	C07 AA05
Drug class	non-cardioselective beta blocker
properties
Molar mass	259.34 g · mol -1 (propranolol) ; 295.80 g · mol -1 (Propranolol Hydrochloride) ;
Melting point	96 ° C (propranolol free base) ; 163–164 ° C (propranolol hydrochloride ) ;
pK s value	9.46
solubility	Water: 61.7 mg l −1 (25 ° C)
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Hydrochloride; Caution
H and P phrases	H: 302
	P: no P-phrases
Toxicological data	660 mg kg −1 ( LD 50 , rat , oral )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Propranolol is a drug from the group of beta blockers and is used, among other things, to treat arterial hypertension (high blood pressure) and cardiac arrhythmias. It was developed in the 1960s by James Whyte Black , who received the Nobel Prize in Medicine in 1988 for his contributions to understanding biochemical principles of drug therapy .

pharmacology

Beta blockers specifically block sympathetic β-adrenoceptors without activating them (no intrinsic activity ). Propranolol is one of the old, non-cardiac selective beta-blockers, in addition to β ₁ -also on β ₂ adrenergic receptors bind.

Side effects

Initial rise in blood pressure,
Triggering asthma attacks ,
Syncope ,
peripheral circulatory disorders.

Pharmacokinetics

The very fat-soluble propranolol is subject to a pronounced first-pass effect , and therefore the bioavailability is only approx. 30%. The breakdown takes place in the liver.

Indications

Propranolol is used like other beta blockers , e.g. B. for the treatment of

arterial hypertension ,
Heart failure ,
coronary artery disease ,
thyrotoxic crisis ,
hypertrophic cardiomyopathy ,
portal hypertension ,
Congenital hemangiomas
for primary prophylaxis of esophageal variceal bleeding and
preoperative therapy of pheochromocytoma (together with alpha blockers ).

In addition, non-selective beta blockers can also be used for migraines and essential tremors (here as the first choice ). In the treatment of post-traumatic stress disorders , propranolol is used as an off-label use against intrusions and hyperexcitability. Another common off-label use of propranolol is its use against physical symptoms of anxiety and against hemangiomas.

research

In vitro , propranolol showed interactions with the membrane proteins of red blood cells , so it may be possible one day to use propranolol for the treatment of malaria .

Stereochemistry

Medicinal products contain the medicinal substance as a racemate (1: 1 mixture of enantiomers ), with the use of the enantiomer which is more effective or which has fewer side effects would be preferred for fundamental reasons. The importance of the enantiomeric purity of synthetically produced active ingredients is being given increasing attention, because the two enantiomers of a chiral medicinal substance almost always show different pharmacology and pharmacokinetics. In the past, this was often ignored due to a lack of knowledge of stereochemical relationships. The active stereoisomer ( eutomer ) is the ( S ) form of propranolol.

Use as a doping agent

Thanks to its property of lowering the heart rate and counteracting the natural physiological tremor, propranolol is also used as a prohibited doping agent in shooting sports. The best known case is the North Korean pistol shooter Kim Jong-su , who was stripped of his silver medal with the free pistol and his bronze medal with the air pistol after a positive test for propranolol at the 2008 Summer Olympics in Beijing.

Trivia

In the GDR , taking an overdose of propranolol ( obsidan ) was a method often used by suicides to kill themselves.

Propranolol has been on the World Health Organization's list of Essential Medicines since 1990 .

Trade names

Monopreparations

Beta-Tablinen (D), Dociton (D), Inderal (A, CH), Obsidan (D), Prophylux (D), Generika (D, CH), Syprol (UK)

Combination preparations

Beta-Turfa (D), Dociretic (D), Dociteren (D), Pertenso (D), Propra comp (D), Triamteren tri-comp (D), Hemangiol

literature

Hasso Scholz, Ulrich Schwabe (ed.): Pocket book of drug treatment: applied pharmacology . 13th edition. Springer, Berlin / Heidelberg 2005, ISBN 3-540-20821-6 .
Björn Lemmer , Kay Brune (eds.): Pharmacotherapy, clinical pharmacology . 14th edition. Springer, Heidelberg 2010, ISBN 978-3-642-10540-1 .

Individual evidence

↑ Propranolol data sheet from AlfaAesar, accessed on February 11, 2010 ( PDF )(JavaScript required) .

↑ ^a ^b ^c ^d Entry on propranolol in the ChemIDplus database of the United States National Library of Medicine (NLM) .

^ The Merck Index . An Encyclopaedia of Chemicals, Drugs and Biologicals. 14th edition, 2006, p. 1348, ISBN 978-0-911910-00-1 .

↑ ^a ^b Data sheet (±) -Propranolol hydrochloride from Sigma-Aldrich , accessed on April 22, 2011 ( PDF ).

↑ James W. Black: Autobiography .

↑ DAZ No. 13 of March 26, 2009.

↑ Christine Léauté-Labrèze, Eric Dumas de la Roque, Thomas Hubiche, Franck Boralevi, Jean-Benoît Thambo, Alain Taïeb: Propranolol for Severe Hemangiomas of Infancy . In: New England Journal of Medicine . tape 358 , no. 24 , 2008, p. 2649-2651 , doi : 10.1056 / NEJMc0708819 , PMID 18550886 (free full text).

↑ Psychiatrierechner.de: Traumatization, post-traumatic stress disorder (PTSD), adjustment disorder, acute stress reaction.

↑ Arzneimittel Telegram 8/1991: “Fear eats the soul” .

^ SC Murphy, T. Harrison, HE Hamm, JW Lomasney, N. Mohandas, K. Haldar: Erythrocyte G protein as a novel target for malarial chemotherapy . In: PLoS medicine . tape 3 , no. 12 , 2006, p. e528 , doi : 10.1371 / journal.pmed.0030528 , PMID 17194200 , PMC 1716186 (free full text).

^ EJ Ariëns: Stereochemistry, a basis for sophisticated nonsense in pharmacokinetics and clinical pharmacology . In: European Journal of Clinical Pharmacology . tape 26 , no. 6 , 1984, pp. 663-668 , doi : 10.1007 / BF00541922 .

↑ Joni Agustiana, Azlina Harun Kamaruddina, Subhash Bhatiaa: Single enantiomeric β-blockers - The existing technologies . In: Process Biochemistry . tape 45 , no. 10 , 2010, p. 1587-1604 , doi : 10.1016 / j.procbio.2010.06.022 .

^ Olympic coverage of the ARD, August 15, 2008: Two new doping cases at the Olympics ( Memento of February 25, 2009 in the Internet Archive ).

↑ DER SPIEGEL: Annals of Death , edition 13/1999.

[alfa-1] Propranolol data sheet from AlfaAesar, accessed on February 11, 2010 ( PDF )(JavaScript required) .

[ChemIDplus-2] Entry on propranolol in the ChemIDplus database of the United States National Library of Medicine (NLM) .

[MerckIndex-3] The Merck Index . An Encyclopaedia of Chemicals, Drugs and Biologicals. 14th edition, 2006, p. 1348, ISBN 978-0-911910-00-1 .

[Sigma-4] Data sheet (±) -Propranolol hydrochloride from Sigma-Aldrich , accessed on April 22, 2011 ( PDF ).

[5] James W. Black: Autobiography .

[6] DAZ No. 13 of March 26, 2009.

[7] Christine Léauté-Labrèze, Eric Dumas de la Roque, Thomas Hubiche, Franck Boralevi, Jean-Benoît Thambo, Alain Taïeb: Propranolol for Severe Hemangiomas of Infancy . In: New England Journal of Medicine . tape 358 , no. 24 , 2008, p. 2649-2651 , doi : 10.1056 / NEJMc0708819 , PMID 18550886 (free full text).

[8] Psychiatrierechner.de: Traumatization, post-traumatic stress disorder (PTSD), adjustment disorder, acute stress reaction.

[9] Arzneimittel Telegram 8/1991: “Fear eats the soul” .

[10] SC Murphy, T. Harrison, HE Hamm, JW Lomasney, N. Mohandas, K. Haldar: Erythrocyte G protein as a novel target for malarial chemotherapy . In: PLoS medicine . tape 3 , no. 12 , 2006, p. e528 , doi : 10.1371 / journal.pmed.0030528 , PMID 17194200 , PMC 1716186 (free full text).

[11] EJ Ariëns: Stereochemistry, a basis for sophisticated nonsense in pharmacokinetics and clinical pharmacology . In: European Journal of Clinical Pharmacology . tape 26 , no. 6 , 1984, pp. 663-668 , doi : 10.1007 / BF00541922 .

[Agustiana-12] Joni Agustiana, Azlina Harun Kamaruddina, Subhash Bhatiaa: Single enantiomeric β-blockers - The existing technologies . In: Process Biochemistry . tape 45 , no. 10 , 2010, p. 1587-1604 , doi : 10.1016 / j.procbio.2010.06.022 .

[13] Olympic coverage of the ARD, August 15, 2008: Two new doping cases at the Olympics ( Memento of February 25, 2009 in the Internet Archive ).

[14] DER SPIEGEL: Annals of Death , edition 13/1999.