Chemistry:Docarpamine

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Docarpamine (INN, JAN), 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.[1][2][3][4][5] It is used orally and intravenously.[6]

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.[4][6][7] There is an intermediate, dideethoxycarbonyldocarpamine (DECD), in which the hydroxyl substitutions have been hydrolyzed.[6] 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.[5][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.[6][8][2] 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.[2]

Although docarpamine is orally active and can achieve therapeutic levels of dopamine in blood,[6] 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.[4][3][10] Its duration of action orally is described as greater than 4 hours.[3]

The drug was first described in the scientific literature by 1980.[1]

See also

  • Neurotransmitter prodrug
  • DA-Phen
  • Dopexamine
  • Ibopamine
  • O,O′-Diacetyldopamine
  • O,O′-Dipivaloyldopamine

References

  1. ↑ 1.0 1.1 The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer US. 2014. p. 463. ISBN 978-1-4757-2085-3. https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA463. Retrieved 13 November 2024. 
  2. ↑ 2.0 2.1 2.2 "DOCARPAMINE". https://drugs.ncats.io/drug/RPQ57D8S72. 
  3. ↑ 3.0 3.1 3.2 Diuretics. Handbook of Experimental Pharmacology. Springer Berlin Heidelberg. 2012. p. 157. ISBN 978-3-642-79565-7. https://books.google.com/books?id=zhHpCAAAQBAJ&pg=PA157. Retrieved 13 November 2024. 
  4. ↑ 4.0 4.1 4.2 Diuretic Agents: Clinical Physiology and Pharmacology. Academic Press. 1997. p. 316. ISBN 978-0-08-053046-8. https://books.google.com/books?id=VHcsrw6unuAC&pg=PA316. Retrieved 13 November 2024. 
  5. ↑ 5.0 5.1 MAO - The Mother of all Amine Oxidases. Journal of Neural Transmission. Supplementa. Springer Vienna. 2013. p. 155. ISBN 978-3-7091-6499-0. https://books.google.com/books?id=XrfrCAAAQBAJ&pg=PA155. Retrieved 13 November 2024. 
  6. ↑ 6.0 6.1 6.2 6.3 6.4 The Future of Pharmaceutical Product Development and Research. Advances in Pharmaceutical Product Development and Research. Academic Press. 2020. p. 207. ISBN 978-0-12-814456-5. https://books.google.com/books?id=H6_SDwAAQBAJ&pg=PA207. Retrieved 13 November 2024. 
  7. ↑ 7.0 7.1 "Prodrug strategies for antihypertensives". Current Topics in Medicinal Chemistry 11 (18): 2299–2317. 2011. doi:10.2174/156802611797183285. PMID 21671866. 
  8. ↑ "Prodrug design to improve pharmacokinetic and drug delivery properties: challenges to the discovery scientists". Current Medicinal Chemistry 17 (32): 3874–3908. 2010. doi:10.2174/092986710793205426. PMID 20858214. 
  9. ↑ "Docarpamine". https://pubchem.ncbi.nlm.nih.gov/compound/71137. 
  10. ↑ A Textbook of In Vitro Fertilization and Assisted Reproduction: The Bourn Hall Guide to Clinical and Laboratory Practice. Taylor & Francis. 2005. p. 245. ISBN 978-1-84214-293-6. https://books.google.com/books?id=AAYuHnPrupUC&pg=PA245. Retrieved 13 November 2024. 



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