{{Short description|Dopamine prodrug}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox drug | drug_name = | image = Docarpamine.svg | image_class = skin-invert-image | width = | caption =
<!-- Clinical data --> | pronounce = | tradename = Tanadopa | Drugs.com = | MedlinePlus = | licence_CA = | licence_EU = | DailyMedID = | licence_US = | pregnancy_AU = | pregnancy_category = | dependency_liability = | addiction_liability = | routes_of_administration = Oral, intravenous<ref name="Tekade2020" /> | class = Dopamine prodrug; Dopamine receptor agonist | ATC_prefix = | ATC_suffix =
<!-- Legal status --> | legal_status =
<!-- Pharmacokinetic data --> | bioavailability = | protein_bound = | metabolism = | metabolites = | onset = | elimination_half-life = | duration_of_action = | excretion =
<!-- Identifiers --> | CAS_number = 74639-40-0 | CAS_supplemental = | PubChem = 71137 | PubChemSubstance = | IUPHAR_ligand = | DrugBank = DB18046 | ChemSpiderID = 64283 | UNII = RPQ57D8S72 | KEGG = D01903 | ChEBI = 31513 | ChEMBL = 2106351 | NIAID_ChemDB = | PDB_ligand = | synonyms = TA-870; TA870; ''N''-(''N''-Acetyl-<small>L</small>-methionyl)-''O'',''O''-bis(ethoxycarbonyl)dopamine
<!-- Chemical data --> | IUPAC_name = [4-[2-<nowiki>[[</nowiki>(2''S'')-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.<ref name="Elks2014">{{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}}</ref><ref name="InxightDrugs">{{cite web | title=DOCARPAMINE | website=Inxight Drugs | url=https://drugs.ncats.io/drug/RPQ57D8S72 | access-date=13 November 2024}}</ref><ref name="BetterGregerBusch2012">{{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}}</ref><ref name="SeldinGiebisch1997">{{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}}</ref><ref name="FinbergYoudimRiederer2013">{{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}}</ref> It is used orally and intravenously.<ref name="Tekade2020">{{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}}</ref>
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.<ref name="SeldinGiebisch1997" /><ref name="Tekade2020" /><ref name="DhaneshwarSharmaPatel2011">{{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 }}</ref> There is an intermediate, dideethoxycarbonyldocarpamine (DECD), in which the hydroxyl substitutions have been hydrolyzed.<ref name="Tekade2020" /> 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.<ref name="FinbergYoudimRiederer2013" /><ref name="DhaneshwarSharmaPatel2011" /> The drug does not cross the blood–brain barrier or affect the central nervous system even at high doses and hence is peripherally selective.<ref name="Tekade2020" /><ref name="JanaMandlekarMarathe2010">{{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 }}</ref><ref name="InxightDrugs" /> The predicted log P (XLogP3) of docarpamine is 2.9.<ref name="PubChem">{{cite web | title=Docarpamine | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/71137 | access-date=13 November 2024}}</ref> It is thought that the therapeutic effects of docarpamine are mediated by activation of peripheral dopamine D<sub>1</sub> receptors.<ref name="InxightDrugs" />
Although docarpamine is orally active and can achieve therapeutic levels of dopamine in blood,<ref name="Tekade2020" /> 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.<ref name="SeldinGiebisch1997" /><ref name="BetterGregerBusch2012" /><ref name="Brinsden2005">{{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}}</ref> Its duration of action orally is described as greater than 4{{nbsp}}hours.<ref name="BetterGregerBusch2012" />
The drug was first described in the scientific literature by 1980.<ref name="Elks2014" />
== See also == * Neurotransmitter prodrug * DA-Phen * Dopexamine * Ibopamine * ''O'',''O''′-Diacetyldopamine * ''O'',''O''′-Dipivaloyldopamine
== References == {{Reflist}}
{{Cardiac stimulants}} {{Dopamine receptor modulators}} {{Phenethylamines}}
Category:Catecholamines Category:Dopamine Category:Dopamine agonists Category:Monoamine precursors Category:Peripherally selective drugs Category:Phenethylamines Category:Prodrugs Category:Ethyl esters Category:Carbonate esters