Docarpamine

{{Short description|Dopamine prodrug}}

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{{Infobox drug

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| image = Docarpamine.svg

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| tradename = Tanadopa

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| routes_of_administration = Oral, intravenous

| class = Dopamine prodrug; Dopamine receptor agonist

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| CAS_number = 74639-40-0

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| PubChem = 71137

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| DrugBank = DB18046

| ChemSpiderID = 64283

| UNII = RPQ57D8S72

| KEGG = D01903

| ChEBI = 31513

| ChEMBL = 2106351

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| synonyms = TA-870; TA870; N-(N-Acetyl-L-methionyl)-O,O-bis(ethoxycarbonyl)dopamine

| IUPAC_name = [4-[2-[[(2S)-2-acetamido-4-methylsulfanylbutanoyl]amino]ethyl]-2-ethoxycarbonyloxyphenyl] ethyl carbonate

| C=21 | H=30 | N=2 | O=8 | S=1

| SMILES = CCOC(=O)OC1=C(C=C(C=C1)CCNC(=O)[C@H](CCSC)NC(=O)C)OC(=O)OCC

| StdInChI = 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

| StdInChIKey = ZLVMAMIPILWYHQ-INIZCTEOSA-N

}}

Docarpamine ({{Abbrlink|INN|International Nonproprietary Name}}, {{Abbrlink|JAN|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.{{cite book | vauthors = Elks J | title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies | publisher=Springer US | year=2014 | isbn=978-1-4757-2085-3 | url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA463 | access-date=13 November 2024 | page=463}}{{cite web | title=DOCARPAMINE | website=Inxight Drugs | url=https://drugs.ncats.io/drug/RPQ57D8S72 | access-date=13 November 2024}}{{cite book | vauthors = Better O, Greger R, Busch A, Knauf H, Dorup J, Mutschler E, Endou H, Greger R, Guder WG, Hosoyamanda M | title=Diuretics | publisher=Springer Berlin Heidelberg | series=Handbook of Experimental Pharmacology | year=2012 | isbn=978-3-642-79565-7 | url=https://books.google.com/books?id=zhHpCAAAQBAJ&pg=PA157 | access-date=13 November 2024 | page=157}}{{cite book | vauthors = Seldin DW, Giebisch GH | title=Diuretic Agents: Clinical Physiology and Pharmacology | publisher=Academic Press | year=1997 | isbn=978-0-08-053046-8 | url=https://books.google.com/books?id=VHcsrw6unuAC&pg=PA316 | access-date=13 November 2024 | page=316}}{{cite book | vauthors = Finberg J, Youdim M, Riederer P, Tipton K | title=MAO - The Mother of all Amine Oxidases | publisher=Springer Vienna | series=Journal of Neural Transmission. Supplementa | year=2013 | isbn=978-3-7091-6499-0 | url=https://books.google.com/books?id=XrfrCAAAQBAJ&pg=PA155 | access-date=13 November 2024 | page=155}} It is used orally and intravenously.{{cite book | vauthors = Tekade RK | title=The Future of Pharmaceutical Product Development and Research | publisher=Academic Press | series=Advances in Pharmaceutical Product Development and Research | year=2020 | isbn=978-0-12-814456-5 | url=https://books.google.com/books?id=H6_SDwAAQBAJ&pg=PA207 | access-date=13 November 2024 | page=207}}

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.{{cite journal | vauthors = Dhaneshwar SS, Sharma M, Patel V, Desai U, Bhojak J | title = Prodrug strategies for antihypertensives | journal = Current Topics in Medicinal Chemistry | volume = 11 | issue = 18 | pages = 2299–2317 | date = 2011 | pmid = 21671866 | doi = 10.2174/156802611797183285 }} There is an intermediate, dideethoxycarbonyldocarpamine (DECD), in which the hydroxyl substitutions have been hydrolyzed. 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. The drug does not cross the blood–brain barrier or affect the central nervous system even at high doses and hence is peripherally selective.{{cite journal | vauthors = Jana S, Mandlekar S, Marathe P | title = Prodrug design to improve pharmacokinetic and drug delivery properties: challenges to the discovery scientists | journal = Current Medicinal Chemistry | volume = 17 | issue = 32 | pages = 3874–3908 | date = 2010 | pmid = 20858214 | doi = 10.2174/092986710793205426 }} The predicted log P (XLogP3) of docarpamine is 2.9.{{cite web | title=Docarpamine | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/71137 | access-date=13 November 2024}} It is thought that the therapeutic effects of docarpamine are mediated by activation of peripheral dopamine D₁ receptors.

Although docarpamine is orally active and can achieve therapeutic levels of dopamine in blood, relatively high doses and frequent administration of the drug (e.g., 600–750{{nbsp}}mg every 8{{nbsp}}hours) are required when it is used by this route.{{cite book | vauthors = Brinsden PR | title=A Textbook of In Vitro Fertilization and Assisted Reproduction: The Bourn Hall Guide to Clinical and Laboratory Practice | publisher=Taylor & Francis | year=2005 | isbn=978-1-84214-293-6 | url=https://books.google.com/books?id=AAYuHnPrupUC&pg=PA245 | access-date=13 November 2024 | page=245}} Its duration of action orally is described as greater than 4{{nbsp}}hours.

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