Isoprenaline

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Structural formula
Structure of isoprenaline
Structural formula without stereochemistry
General
Non-proprietary name Isoprenaline
other names
  • (±) -Isoproterenol
  • DL -1- (3,4-dihydroxyphenyl) -2-isopropylaminoethanol
  • ( RS ) -1- (3,4-dihydroxyphenyl) -2-isopropylaminoethanol
  • (±) -1- (3,4-Dihydroxyphenyl) -2-isopropylaminoethanol
  • rac -1- (3,4-dihydroxyphenyl) -2-isopropylaminoethanol
Molecular formula C 11 H 17 NO 3
External identifiers / databases
CAS number 7683-59-2
EC number 231-687-7
ECHA InfoCard 100.028.807
PubChem 3779
ChemSpider 3647
DrugBank DB01064
Wikidata Q415550
Drug information
ATC code
Drug class

Sympathomimetic

Mechanism of action

β-adrenoceptor - agonist

properties
Molar mass 211.26 g · mol -1
Physical state

firmly

Melting point

155.5 ° C

pK s value

8.64

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS hazard labeling
no classification available
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Isoprenaline or isoproterenol is a structural isomer to orciprenaline a synthetic racemic noradrenaline - derivative , as the sympathomimetic agent is used. The drug was patented by Boehringer Ingelheim in 1943 .

pharmacology

As a catecholamine, isoprenaline is an adrenaline- like substance that only activates β-adrenoceptors , while noradrenaline has a high affinity for α-adrenoceptors. The N -isopropyl substituent is responsible for this selectivity, at the same time an optimum of β-adrenoceptor affinity is achieved.

It causes the bronchial and vascular muscles to relax, as well as (in adults dosed at 1–5 µg / min) an increase in the contraction force and beat frequency of the heart as well as a decrease in blood pressure (while the systolic blood pressure increases slightly, the diastolic pressure decreases sharply, which overall leads to a decrease in mean arterial pressure). The pronounced effect on the heart occurs through the stimulation of the β 1 -adrenoceptors , and renin is also released from the kidney cortex. The enzyme adenylyl cyclase , which catalyzes the synthesis of cyclic adenosine monophosphate (cAMP) , which leads to an increased production of the same, is activated via the receptors . Due to the increased cAMP concentration, the enzyme protein kinase A is activated , which leads to the phosphorylation of voltage-dependent calcium ion channels . These are responsible for an increase in the slow Ca 2+ inward current during cell depolarization . The increased concentration of Ca 2+ results in the increased heart rate. The heartbeat and the conduction of excitation are accelerated, especially in the AV node , because the increase in the slow influx of Na + and Ca 2+ ions accelerates the spontaneous diastolic depolarization in all heart sections.

In addition, isoprenaline slows down the antigen-induced release of the messenger substance histamine , which slows down the transmission of anaphylaxis , and increases the production of lactates . It also has a relaxing effect on the uterus (tocolysis).

It is compatible with almost all common solutions for intravenous injection, with the exception of sodium hydrogen carbonate . In the treatment of bronchial asthma , local application in the form of an aerosol is preferred to systemic administration, since the onset of action occurs earlier and the systemic effect, the excitation of β 1 -adrenoceptors, is less.

The administration of isoprenaline is contraindicated in hyperthyroidism , coronary and arteriosclerosis , as well as in cardiac insufficiency , tachycardiac arrhythmias and arterial hypertension .

Stereochemistry

Isoprenaline is used as a 1: 1 mixture (racemate) of the ( R ) - and ( S ) -enantiomers, although the importance of the enantiomeric purity of the synthetically produced active ingredients is increasingly being paid attention, because the two enantiomers of a chiral drug almost always show a different one Pharmacology and pharmacokinetics. In the past, this was often ignored due to a lack of knowledge of stereochemical relationships. For fundamental considerations, it would be preferable to use the enantiomer which is more effective or has fewer side effects. The ( R ) - and the ( S ) -isomers of isoprenaline bind significantly differently to human serum proteins.

Drug market

There are no finished medicinal products with this active ingredient available in Germany.

literature

  • 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. 46 f.

Individual evidence

  1. a b entry on isoprenaline. In: Römpp Online . Georg Thieme Verlag, accessed on December 28, 2014.
  2. This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
  3. 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 , pp. 44-47 and 76.
  4. EJ Ariëns, Stereochemistry, a basis for sophisticated nonsense in pharmacokinetics and clinical pharmacology , European Journal of Clinical Pharmacology 26 (1984) 663-668, doi : 10.1007 / BF00541922 .
  5. G. Sager, D. Sandnes, A. Bessesen and S. Jacobsen: Andrenergic ligand binding in human serum , Biochemical Pharmacology 34 (1985) 2812.
  6. Federal Drug Information System - accessed on December 25, 2012.