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.[2][3][4][5][6] It is used orally and intravenously.[1]
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| Trade names | Tanadopa |
| Other names | TA-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 |
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| Formula | C21H30N2O8S |
| Molar mass | 470.54 g·mol−1 |
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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
editReferences
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- ^ a b Elks J (2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer US. p. 463. ISBN 978-1-4757-2085-3. Retrieved 13 November 2024.
- ^ a b c "DOCARPAMINE". Inxight Drugs. Retrieved 13 November 2024.
- ^ a b c Better O, Greger R, Busch A, Knauf H, Dorup J, Mutschler E, et al. (2012). Diuretics. Handbook of Experimental Pharmacology. Springer Berlin Heidelberg. p. 157. ISBN 978-3-642-79565-7. Retrieved 13 November 2024.
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- ^ a b Finberg J, Youdim M, Riederer P, Tipton K (2013). MAO - The Mother of all Amine Oxidases. Journal of Neural Transmission. Supplementa. Springer Vienna. p. 155. ISBN 978-3-7091-6499-0. Retrieved 13 November 2024.
- ^ a b Dhaneshwar SS, Sharma M, Patel V, Desai U, Bhojak J (2011). "Prodrug strategies for antihypertensives". Current Topics in Medicinal Chemistry. 11 (18): 2299–2317. doi:10.2174/156802611797183285. PMID 21671866.
- ^ Jana S, Mandlekar S, Marathe P (2010). "Prodrug design to improve pharmacokinetic and drug delivery properties: challenges to the discovery scientists". Current Medicinal Chemistry. 17 (32): 3874–3908. doi:10.2174/092986710793205426. PMID 20858214.
- ^ "Docarpamine". PubChem. Retrieved 13 November 2024.
- ^ 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.