Molsidomine

Source: Wikipedia, the free encyclopedia.
Molsidomine
intravenous infusion
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
renal
Identifiers
  • 1-Ethoxy-N-(3-morpholino-5-oxadiazol-3-iumyl)methanimidate
JSmol)
Melting point140 to 141 °C (284 to 286 °F)
  • [O-]C(OCC)=Nc2on[n+](N1CCOCC1)c2
  • InChI=1S/C9H14N4O4/c1-2-16-9(14)10-8-7-13(11-17-8)12-3-5-15-6-4-12/h7H,2-6H2,1H3 checkY
  • Key:XLFWDASMENKTKL-UHFFFAOYSA-N checkY

Molsidomine (trade names Corvasal, Corvaton and many others) is an orally active, long acting

angina pectoris. Molsidomine is metabolized in the liver to the active metabolite linsidomine. Linsidomine is an unstable compound that releases nitric oxide (NO) upon decay as the actual vasodilating compound.[1]

Medical uses

Molsidomine is used for the prevention and long-term treatment of stable and unstable angina pectoris, with or without

left heart failure. It is also used to treat angina in the context of an acute myocardial infarction.[2][3]

Contraindications

The drug must not be used in patients with acute cardiac arrest or severe hypotension (low blood pressure), during lactation, and in combination with PDE5 inhibitors such as sildenafil.[2][3]

Side effects

The most common adverse effects are headache, which occurs in 10–25% of patients, and low blood pressure. Side effects occurring in fewer than 1% of patients include dizziness,

reflex tachycardia (fast heartbeat), hypersensitivity reactions, as well as thrombocytopenia (low blood platelet count) in rare cases.[2][3]

Interactions

The blood pressure lowering effect of molsidomine can be amplified significantly by PDE5 inhibitors, potentially leading to fainting or myocardial infarction, and to a lesser extent by other

antihypertensive drugs such as beta blockers, calcium channel blockers, or other nitrovasodilators. Ergolines can antagonise the effects of molsidomine.[2][3]

Pharmacology

Mechanism of action

Further information: Biological functions of nitric oxide

Molsidomine belongs to the drug class of

blood vessels.[4][5]

Pharmacokinetics

The substance is quickly and almost completely (>90%) absorbed from the gut. Molsidomine is a

plasma proteins. Both molsidomine and linsidomine reach their highest concentrations in the blood plasma after one to two hours. Linsidomine has a biological half-life of one to two hours. More than 90% are excreted via the kidney.[2][4]

NO release from molsidomine[4]

Chemistry

mesoionic
structure of molsidomine

Molsidomine and linsidomine are

absorption maximum is in the near ultraviolet, at 326 nm, in chloroform. The substance is sensitive to ultraviolet light at wavelengths shorter than 320 nm.[3]

Synthesis

Thieme Synthesis:[6] Patents:[7]

Its synthesis starts by reacting 1-aminomorpholine with formaldehyde and hydrogen cyanide to give 2. Nitrosation gives the N-nitroso analog (3) which cyclizes to the Linsidomine (4) on treatment with anhydrous acid. Formation of the ethyl urethane is then made possible by reacting linsidomine with ethyl chloroformate.

Also see a related structure called Ciclosidomine.

History

The substance was first synthesised at Takeda in 1970. Its antihypertensive and vasodilating properties were discovered the same year.[8]

References

  1. PMID 8743336
    .
  2. ^
    ISBN 978-3-85200-196-8
    .
  3. ^
    ISBN 978-3-7741-9846-3
    .
  4. ^
    ISBN 978-3-8047-1763-3
    .
  5. ISBN 978-0-7167-2009-6
    .
  6. ^ Chemical and Pharmaceutical Bulletin 19(1), 72-79, 1971-01-25.
  7. ^ DE1695897 idem K Masuda & Y Imashiro, U.S. patent 3,769,283 & US3812128 (1973 & 1974 to Takeda Pharmaceutical Co Ltd).
  8. ISBN 9783804721135
    .
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