Isradipine

Structural formula
	Simplified structural formula - ; a mixture of two atropisomers
General
Non-proprietary name	Isradipine
other names	4- (4-Benzofurazanyl) -1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid methyl 1-methylethyl ester ( IUPAC )
Molecular formula	C 19 H 21 N 3 O 5
External identifiers / databases
EC number	630-420-5
ECHA InfoCard	100.158.721
PubChem	3784
DrugBank	DB00270
Wikidata	Q414873
Drug information
ATC code	C08 CA02
Drug class	Antihypertensive agent
Mechanism of action	Calcium antagonist
properties
Molar mass	371.39 g · mol -1
Physical state	firmly
Melting point	168-170 ° C (racemate) S (+) 142 ° C; R (-) 140 ° 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	no GHS pictograms
	no GHS pictograms
H and P phrases	H: no H-phrases
	P: no P-phrases
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Isradipine is a drug belonging to the class of calcium antagonists of the dihydropyridine type , which is used as an antihypertensive agent. As a special structural feature it has a benzo- oxadiazole ring (outdated benzo- furazan ).

Isradipine is well absorbed through the intestine, but is subject to a pronounced first-pass effect , so that the bioavailability is given as 15-24%. A maximum plasma concentration is reached after 0.4 to 2.5 hours; the half-life is about 9 hours. The enzyme cytochrome P450 3A4 is involved in the breakdown.

Appearance and properties

According to Heitzmann, isradipine is obtained in good yield from 2,1,3-benzoxadiazole by reaction with LDA in dimethylformamide and heating the 2,1,3-benzoxadiazole aldehyde formed with aminocrotonic acid methyl ester and isopropyl acetoacetate in isopropanol . The crystalline, yellow substance consists of a mixture of the ( S ) - (+) - and the ( R ) - (-) - form, which melts at 168–170 ° C and decomposes when exposed to light and air and when heated. Therefore it is stored in the dark at 2–8 ° C under a nitrogen atmosphere.

Stereochemistry

Isradipine contains a stereocenter and consists of two enantiomers , more precisely atropisomers . This is a racemate , i.e. a 1: 1 mixture of ( R ) - and ( S ) -form:

Enantiomers of isradipine
CAS number: 84260-63-9	CAS number: 84260-64-0

Effects, absorption and elimination

The calcium antagonist, similar to nifedipine, with a high affinity for calcium channels in the smooth arterial vascular musculature causes a very selective reduction in the tone of the smooth vascular musculature. Studies have shown that the substance has a natriuretic ( sodium excreting ) effect in addition to its vasodilatory effect and that left ventricular hypertrophy regresses with isradipine therapy. When administered orally, 90–95% of the drug is absorbed in the intestine and 97% is bound to plasma protein . In animal experiments, isradipine was able to penetrate the blood-brain barrier . When used in human medicine, the substance is completely metabolized and 60–65% excreted via the kidneys and 25–30% via the faeces .

Trade names

Monopreparations

Lomir (A, CH), Vascal (D)

Individual evidence

↑ ^a ^b ^c ^d ^e H. Hager, F. von Bruchhausen, P. Surmann, W. Blaschek, E. Nürnberg: Hagers Handbuch Der Pharmazeutischen Praxis , 1999, Springer-Verlag, ISBN 3-540-52640-4 .

↑ ^a ^b Isradipine data sheet from Sigma-Aldrich , accessed on May 25, 2011 ( PDF ).

↑ ^a ^b Entry on Isradipine in the DrugBank of the University of Alberta .

↑ M. Heitzmann ( Sandoz AG ), CH 661270, 1987, cit. according to CA 108: 94566n.

↑ Rote Liste Service GmbH (Ed.): Rote Liste 2017 - drug directory for Germany (including EU approvals and certain medical devices) . Rote Liste Service GmbH, Frankfurt / Main, 2017, edition 57, ISBN 978-3-946057-10-9 , p. 193.

↑ Red List online, as of October 2009.

↑ AM com. d. Switzerland, as of October 2009.

↑ AGES-PharmMed, as of October 2009.

[Hager-1] H. Hager, F. von Bruchhausen, P. Surmann, W. Blaschek, E. Nürnberg: Hagers Handbuch Der Pharmazeutischen Praxis , 1999, Springer-Verlag, ISBN 3-540-52640-4 .