Molsidomine

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Structural formula
Molsidomine structural formula
Mesomeric boundary structures
General
Non-proprietary name Molsidomine
other names

N - (ethoxycarbonyl) -3- (4-morpholinyl) sydnonimine

Molecular formula C 9 H 14 N 4 O 4
External identifiers / databases
CAS number 25717-80-0
EC number 247-207-4
ECHA InfoCard 100.042.902
PubChem 5353788
ChemSpider 24608574
DrugBank DB09282
Wikidata Q408132
Drug information
ATC code

C01 DX12

Drug class

Vasodilator

Mechanism of action

Vascular dilatation by splitting off nitric oxide

properties
Molar mass 242.2 g mol −1
Physical state

firmly

Melting point

140-141 ° C

pK s value

3.0

solubility

Slightly soluble in water, soluble in dilute hydrochloric acid

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
07 - Warning

Caution

H and P phrases H: 302
P: no P-phrases
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Molsidomine belongs to the group of non-enzymatic nitric oxide donors . This drug releases nitric oxide (NO) and thus leads to vascular dilation with a reduction in the wall tension of the coronary arteries. It is therefore used for the treatment of angina pectoris in coronary heart disease and for the treatment of acutely decompensated heart failure .

Molsidomine was first synthesized in 1970 by K. Masuda at Takeda . In the same year, K. Kikuchi observed the antihypertensive and antianginal effects.

Pharmacokinetics

Molsidomine is an inactive precursor ( prodrug ). It is not itself responsible for the vasodilating effect, but is metabolized in the liver to linsidomine (SIN-1) . This changes into the open-ring form without the action of enzymes and the actual active substance nitrogen monoxide is split off. Since no enzymes are required for the formation of free nitrogen monoxide, there is no weakening of the effect even with long-term administration ( nitrate tolerance ). Molsidomine inhibits platelet adhesion to a small extent . However, this effect is of no clinical relevance due to the small effect .

Molsidomine.svg→ SIN-1.svg→ SIN-1A chemical structure.svg→ NO

Molsidomine → Linsidomine (SIN-1) → SIN-1A → Nitric oxide

Pharmacodynamics

The release of nitric oxide leads to a dilatation of the coronary arteries, the large vena cava and the pulmonary vessels, thereby reducing the load on the heart. According to the Frank Starling mechanism , this leads to a decrease in the blood filling of the heart, the heart wall is no longer stretched as much and thus oxygen consumption is reduced. Because the more the heart wall is stretched, the more work it does. The widening of the coronary vessels and the decrease in filling lead to better blood flow to the heart wall and thus to an improvement in the oxygen supply to the heart muscles .

The directly active substance, linsidomine, is also available for direct intravenous therapy.

application

Molsidomin is therapeutically prescribed for the prophylaxis of angina pectoris attacks. Acute therapy is not possible with molsidomine, as the maximum effect is only achieved after 30 to 60 minutes.

Side effects

The most important side effects are headache, dizziness and a drop in blood pressure due to the severe vasodilation.

In animal experiments with rats, higher doses of molsidomine resulted in an increased number of malignant nasal tumors.

Trade names

Monopreparations

Corvaton (D, CH), Molsibeta (D), Molsidolat (A), Molsiket (D), Molsi-Puren (D), various generics (D)

Individual evidence

  1. ^ The Merck Index . An Encyclopaedia of Chemicals, Drugs and Biologicals. 14th edition. 2006, ISBN 0-911910-00-X , pp. 1076-1077.
  2. ↑ a b c d e entry on molsidomine. In: Römpp Online . Georg Thieme Verlag, accessed on July 16, 2019.
  3. ↑ a b Molsidomine data sheet from Sigma-Aldrich , accessed on April 10, 2011 ( PDF ).
  4. ↑ German Medical Association (BÄK), National Association of Statutory Health Insurance Physicians (KBV), Working Group of Scientific Medical Societies (AWMF): National Care Guideline for Chronic Heart Failure - Long Version. 2017; Version 2.
  5. ^ 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 .
  6. ↑ Red List online, as of September 2009.
  7. ↑ Am Comp. d. Switzerland, as of September 2009.
  8. ↑ AGES-Pharmmed, as of September 2009.

literature