Quinidine

Structural formula
General
Surname	Quinidine
other names	(+) - (9 S ) -6′-methoxycinchonan-9-ol; (+) - quinidine;
Molecular formula	C 20 H 24 N 2 O 2 (quinidine) ; C 20 H 24 N 2 O 2 · H 2 SO 4 · H 2 O (quinidine · H 2 SO 4 · H 2 O) ;
Brief description	colorless, crystalline solid
External identifiers / databases
EC number	200-279-0
ECHA InfoCard	100,000,254
PubChem	441074
ChemSpider	389880
DrugBank	DB00908
Wikidata	Q412496
Drug information
ATC code	C01 BA01
Drug class	Antiarrhythmic
properties
Molar mass	324.43 g mol −1 (quinidine) ; 782.94 g mol −1 (quinidine H 2 SO 4 H 2 O) ;
Physical state	firmly
Melting point	174-175 ° C (quinidine)
solubility	poor in water (0.5 g l −1 at 20 ° C, quinidine)
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances danger
H and P phrases	H: 301-317
	P: 261-270-280-301 + 310-302 + 352-333 + 313
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Quinidine (English quinidine ) is a chemical compound and belongs to the natural group of quinoline alkaloids . Quinidine sulfate is used as a medicinal substance.

history

Quinidine is considered to be the first effective antiarrhythmic . It was discovered in 1847 by Ferdinand Ludwig Winckler (1801–1868), but its effect against arrhythmias could only be demonstrated in 1918 by Maximilian Rupert Franz von Frey (1852–1932). He demonstrated the effectiveness in atrial fibrillation .

Occurrence

Quinoline alkaloids, including (+) - quinidine, are found in the bark of the cinchona tree.

The quinidine can be obtained from the bark of the cinchona tree .

structure

Quinidine is a diastereomer of quinine and has a (8 R , 9 S ) configuration [quinine has (8 S , 9 R ) configuration]. The configuration at the carbon atom to which the vinyl group is attached is the same for these two chiral compounds.

use

Quinidine is used as an intravenous and oral antiarrhythmic (class 1A according to Vaughan Williams) for atrial fibrillation , extrasystoles and ventricular tachyarrhythmias. Its effect is based on binding to open sodium channels. The effectiveness depends on the frequency, as the ion channel quinidine complex only dissolves slowly. In addition, the substance also reduces the potassium conductivity, which leads to a lengthening of the action potential duration . In contrast to sodium conductivity, this effect decreases with higher frequency. Quinidine also inhibits calcium channels in the heart muscles and has atropine-like effects . This anticholinergic effect also partially antagonizes the effect, so the heart rate can increase with low doses and the conduction can be improved. At high doses, quinidine blocks atrioventricular transmission.

Quinidine is well absorbed after oral administration. The half-life is about 5 hours and excretion is mainly via the kidneys.

Due to its pronounced side effects ( QTc time lengthening , AV block , torsade de pointes , ventricular tachycardias and gastrointestinal complaints due to its atropine-like effect), it is only rarely used today. When given intravenously, quinidine causes a strong decrease in vascular resistance.

Combination with other drugs that have a cardio-depressive effect should definitely be avoided, as it can lead to a strong increase in side effects. When combined with digoxin , its plasma level rises sharply. When combined with loperamide , a blockage of the P-glycoprotein at the blood-brain barrier can lead to respiratory depression.

It was sold in Germany in combination with Verapamil by Abbott under the name Cordichin until 2018 .

Individual evidence

↑ ^a ^b ^c Entry on quinidine in the GESTIS substance database of the IFA , accessed on January 9, 2019(JavaScript required) .
^ ^A ^b The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals , 14th Edition (Merck & Co., Inc.), Whitehouse Station, NJ, USA, 2006, ISBN 978-0-911910-00-1 , Pp. 1385-1386.
^ Wolf-Dieter Müller-Jahncke , Christoph Friedrich , Ulrich Meyer: Medicinal history . 2., revised. and exp. Ed. Wiss. Verl.-Ges, Stuttgart 2005, ISBN 978-3-8047-2113-5 , pp. 163 .
^ Albert Gossauer: Structure and Reactivity of Biomolecules , Verlag Helvetica Chimica Acta, Zurich 2006, ISBN 978-3-906390-29-1 , p. 495.
↑ Reinhard Larsen: Anesthesia and intensive medicine in cardiac, thoracic and vascular surgery. (1st edition 1986) 5th edition. Springer, Berlin / Heidelberg / New York et al. 1999, ISBN 3-540-65024-5 , p. 73.
↑ Aktories: General and special pharmacology and toxicology , 9th edition.
↑ Red List online, as of September 2009.

[GESTIS-1] Entry on quinidine in the GESTIS substance database of the IFA , accessed on January 9, 2019(JavaScript required) .

[MERCK_Index-2] A ^b The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals , 14th Edition (Merck & Co., Inc.), Whitehouse Station, NJ, USA, 2006, ISBN 978-0-911910-00-1 , Pp. 1385-1386.

[3] Wolf-Dieter Müller-Jahncke , Christoph Friedrich , Ulrich Meyer: Medicinal history . 2., revised. and exp. Ed. Wiss. Verl.-Ges, Stuttgart 2005, ISBN 978-3-8047-2113-5 , pp. 163 .

[Gossauer-4] Albert Gossauer: Structure and Reactivity of Biomolecules , Verlag Helvetica Chimica Acta, Zurich 2006, ISBN 978-3-906390-29-1 , p. 495.

[5] Reinhard Larsen: Anesthesia and intensive medicine in cardiac, thoracic and vascular surgery. (1st edition 1986) 5th edition. Springer, Berlin / Heidelberg / New York et al. 1999, ISBN 3-540-65024-5 , p. 73.

[6] Aktories: General and special pharmacology and toxicology , 9th edition.

[7] Red List online, as of September 2009.