Docarpamine

Last updated

Docarpamine
Docarpamine.svg
Clinical data
Trade names Tanadopa
Other namesTA-870; TA870; N-(N-Acetyl-L-methionyl)-O,O-bis(ethoxycarbonyl)dopamine
Routes of
administration 		Oral, intravenous [1]
Drug class Dopamine prodrug; Dopamine receptor agonist
Identifiers
  • [4-[2-[[(2S)-2-acetamido-4-methylsulfanylbutanoyl]amino]ethyl]-2-ethoxycarbonyloxyphenyl] ethyl carbonate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C21H30N2O8S
Molar mass 470.54 g·mol−1
3D model (JSmol)
  • CCOC(=O)OC1=C(C=C(C=C1)CCNC(=O)[C@H](CCSC)NC(=O)C)OC(=O)OCC
  • InChI=1S/C21H30N2O8S/c1-5-28-20(26)30-17-8-7-15(13-18(17)31-21(27)29-6-2)9-11-22-19(25)16(10-12-32-4)23-14(3)24/h7-8,13,16H,5-6,9-12H2,1-4H3,(H,22,25)(H,23,24)/t16-/m0/s1
  • Key:ZLVMAMIPILWYHQ-INIZCTEOSA-N

Docarpamine (INN Tooltip International Nonproprietary Name, JAN Tooltip Japanese Accepted Name), sold under the brand name Tanadopa, is an orally active dopamine prodrug which is marketed in Japan for the treatment of acute cardiac insufficiency and/or chronic heart failure. [2] [3] [4] [5] [6] It is used orally and intravenously. [1]

In terms of bioactivation, the hydroxyl groups of docarpamine are freed by esterases in the gut and liver and the amino group is freed by γ-glutamyltransferase in the kidney and liver. [5] [1] [7] There is an intermediate, dideethoxycarbonyldocarpamine (DECD), in which the hydroxyl substitutions have been hydrolyzed. [1] The N-substitution protects the drug from first-pass metabolism by monoamine oxidase (MAO) until it is cleaved into dopamine and allows it to be orally active. [6] [7] The drug does not cross the blood–brain barrier or affect the central nervous system even at high doses and hence is peripherally selective. [1] [8] [3] The predicted log P (XLogP3) of docarpamine is 2.9. [9] It is thought that the therapeutic effects of docarpamine are mediated by activation of peripheral dopamine D1 receptors. [3]

Although docarpamine is orally active and can achieve therapeutic levels of dopamine in blood, [1] relatively high doses and frequent administration of the drug (e.g., 600–750 mg every 8 hours) are required when it is used by this route. [5] [4] [10] Its duration of action orally is described as greater than 4 hours. [4]

The drug was first described in the scientific literature by 1980. [2]

See also

Related Research Articles

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References

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  9. ↑ "Docarpamine". PubChem. Retrieved 13 November 2024.
  10. ↑ Brinsden PR (2005). A Textbook of In Vitro Fertilization and Assisted Reproduction: The Bourn Hall Guide to Clinical and Laboratory Practice. Taylor & Francis. p. 245. ISBN   978-1-84214-293-6 . Retrieved 13 November 2024.
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