Docarpamine - Misplaced Pages

Dopamine prodrug

Pharmaceutical compound

Docarpamine
Clinical data

Trade names	Tanadopa
Other names	TA-870; TA870; N-(N-Acetyl-L-methionyl)-O,O-bis(ethoxycarbonyl)dopamine
Routes of administration	Oral, intravenous
Drug class	Dopamine prodrug; Dopamine receptor agonist
Identifiers
IUPAC name amino]ethyl]-2-ethoxycarbonyloxyphenyl] ethyl carbonate
CAS Number	74639-40-0
PubChem CID	71137
DrugBank	DB18046
ChemSpider	64283
UNII	RPQ57D8S72
KEGG	D01903
ChEBI	CHEBI:31513
ChEMBL	ChEMBL2106351
CompTox Dashboard (EPA)	DTXSID1057820
Chemical and physical data
Formula	C₂₁H₃₀N₂O₈S
Molar mass	470.54 g·mol
3D model (JSmol)	Interactive image
SMILES CCOC(=O)OC1=C(C=C(C=C1)CCNC(=O)(CCSC)NC(=O)C)OC(=O)OCC
InChI 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 (INNTooltip International Nonproprietary Name, JANTooltip 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. It is used orally and intravenously.

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. 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. The predicted log P (XLogP3) of docarpamine is 2.9. 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 mg every 8 hours) are required when it is used by this route. Its duration of action orally is described as greater than 4 hours.

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

References

^ Tekade RK (2020). The Future of Pharmaceutical Product Development and Research. Advances in Pharmaceutical Product Development and Research. Academic Press. p. 207. ISBN 978-0-12-814456-5. Retrieved 13 November 2024.
^ 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.
^ "DOCARPAMINE". Inxight Drugs. Retrieved 13 November 2024.
^ 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.
^ Seldin DW, Giebisch GH (1997). Diuretic Agents: Clinical Physiology and Pharmacology. Academic Press. p. 316. ISBN 978-0-08-053046-8. Retrieved 13 November 2024.
^ 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.
^ 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.

Cardiac stimulants excluding cardiac glycosides (C01C)

Adrenergic and
dopaminergic agents

Adrenergic agonists

α	Denopamine Metaraminol Methoxamine Midodrine Norfenefrine Oxedrine Phenylephrine
β	Arbutamine Dobutamine Isoprenaline Prenalterol
mixed	Amezinium metilsulfate Droxidopa Epinephrine # Etilefrine Norepinephrine

Dopamine agonists

Fenoldopam

Both

Unknown/ungrouped

Phosphodiesterase inhibitors (PDE3I)

Other cardiac stimulants

WHO-EM
Withdrawn from market
Clinical trials:
- Phase III
- Never to phase III

Dopamine receptor modulators

D₁-like

Agonists

Phenethylamines: BCO-001
Deoxyepinephrine (N-methyldopamine, epinine)
Dopexamine
Etilevodopa
Ibopamine
L-DOPA (levodopa)
Melevodopa
L-Phenylalanine
L-Tyrosine
XP21279

PAMs

Tetrahydroisoquinolines: DETQ
DPTQ
Mevidalen

Antagonists

Typical antipsychotics: Butaclamol
Chlorpromazine
Chlorprothixene
Flupentixol (flupenthixol) (+melitracen)
Fluphenazine
Loxapine
Perphenazine (+amitriptyline)
Pifluthixol
Thioridazine
Thiothixene
Trifluoperazine (+tranylcypromine)
Zuclopenthixol

D₂-like

Agonists

Phenethylamines: Deoxyepinephrine (N-methyldopamine, epinine)
Dopexamine
Etilevodopa
Ibopamine
L-DOPA (levodopa)
L-Phenylalanine
L-Tyrosine
Melevodopa
XP21279

Atypical antipsychotics: Alentemol (U-66444B)
Aripiprazole (+sertraline)
Aripiprazole lauroxil
Bifeprunox
Brexpiprazole
Brilaroxazine
Cariprazine
F-15063
Lumateperone
Norclozapine

Antagonists

Typical antipsychotics: Acepromazine
Acetophenazine
Azaperone
Benperidol
Bromperidol
Butaclamol
Butaperazine
Chloracizine
Chlorproethazine
Chlorpromazine
Chlorprothixene
Ciclindole
Clopenthixol
Clothixamide
Clopimozide
Droperidol
Fluacizine
Fluanisone
Flucindole
Fluotracen
Flupentixol (flupenthixol) (+melitracen)
Fluphenazine
Fluprothixene
Fluspirilene
Haloperidol
Homopipramol
Lenperone
Levomepromazine (methotrimeprazine)
Levosulpiride
Loxapine
Mesoridazine
Moperone
Naranol
Nemonapride
Penfluridol
Perathiepin
Perazine
Pericyazine (periciazine)
Perphenazine (+amitriptyline)
Piflutixol (pifluthixol)
Pimozide
Pipamperone
Preclamol
Prochlorperazine
Promazine
Prothipendyl
Spiperone (spiroperidol)
Sulforidazine
Sulpiride
Sultopride
Teflutixol
Thiopropazate
Thioproperazine
Thioridazine
Thiothixene
Timiperone
Trifluoperazine (+tranylcypromine)
Triflupromazine
Trifluperidol
Zetidoline
Zuclopenthixol

Antiemetics/gastroprokinetics/sedatives: Aceprometazine
AS-8112
Alimemazine
Alizapride
Benzquinamide
Bromopride
Clebopride
Deudomperidone
Domperidone
Eticlopride
Hydroxyzine
Itopride
Metoclopramide
Metopimazine
Promethazine
Thiethylperazine
Trazpiroben
Trimethobenzamide

See also: Receptor/signaling modulators
Adrenergics
Serotonergics
Monoamine reuptake inhibitors
Monoamine releasing agents
Monoamine metabolism modulators
Monoamine neurotoxins

v t e Phenethylamines
Phenethylamines	Psychedelics: 25B-NBOMe 25C-NBOMe 25D-NBOMe 25I-NBOMe 25N-NBOMe 2C-B 2C-B-AN 2C-Bn 2C-Bu 2C-C 2C-CN 2C-CP 2C-D 2C-E 2C-EF 2C-F 2C-G 2C-G-1 2C-G-2 2C-G-3 2C-G-4 2C-G-5 2C-G-6 2C-G-N 2C-H 2C-I 2C-iP 2C-N 2C-NH2 2C-O 2C-O-4 2C-P 2C-Ph 2C-SE 2C-T 2C-T-2 2C-T-3 2C-T-4 2C-T-5 2C-T-6 2C-T-7 2C-T-8 2C-T-9 2C-T-10 2C-T-11 2C-T-12 2C-T-13 2C-T-14 2C-T-15 2C-T-16 2C-T-17 2C-T-18 2C-T-19 2C-T-20 2C-T-21 2C-T-22 2C-T-22.5 2C-T-23 2C-T-24 2C-T-25 2C-T-27 2C-T-28 2C-T-30 2C-T-31 2C-T-32 2C-T-33 2C-TFE 2C-TFM 2C-YN 2C-V Allylescaline DESOXY Escaline Isoproscaline Jimscaline Macromerine MEPEA Mescaline Metaescaline Methallylescaline Proscaline Psi-2C-T-4 TCB-2 Stimulants: Phenylethanolamine Hordenine Phenethylamine Phenpromethamine α-Methylphenethylamine (amphetamine) β-Methylphenethylamine m-Methylphenethylamine N-Methylphenethylamine o-Methylphenethylamine p-Methylphenethylamine Methylphenidate Entactogens: Lophophine MDPEA MDMPEA Others: BOH DMPEA
Amphetamines	Psychedelics: 3C-AL 3C-BZ 3C-E 3C-MAL 3C-P Aleph Beatrice Bromo-DragonFLY D-Deprenyl DMA DMCPA DMMDA DOB DOC DOEF DOET DOI DOM DON DOPR DOTFM Ganesha MMDA MMDA-2 Psi-DOM TMA TeMA ZDCM-04 Stimulants: 2-FA 2-FMA 3-FA 3-FMA Acridorex Alfetamine Amfecloral Amfepentorex Amphetamine (Dextroamphetamine, Levoamphetamine) Amphetaminil Benfluorex Benzphetamine Cathine Clobenzorex Dimethylamphetamine Ephedrine Etilamfetamine Fencamfamin Fencamine Fenethylline Fenfluramine (Dexfenfluramine, Levofenfluramine) Fenproporex Flucetorex Fludorex Formetorex Furfenorex Gepefrine 4-Hydroxyamphetamine Iofetamine Isopropylamphetamine Lefetamine Lisdexamfetamine Mefenorex Metaraminol Methamphetamine (Dextromethamphetamine, Levomethamphetamine) Methoxyphenamine MMA Morforex Norfenfluramine L-Norpseudoephedrine N,alpha-Diethylphenylethylamine Oxifentorex Oxilofrine Ortetamine PBA PCA PFA PFMA PIA PMA PMEA PMMA Phenylpropanolamine Pholedrine Prenylamine Propylamphetamine Pseudoephedrine Sibutramine Tiflorex Tranylcypromine Xylopropamine Zylofuramine Entactogens: 4-FA 4-FMA 4-MA 4-MMA 4-MTA 5-APB 5-APDB 5-EAPB 5-IT 5-MAPB 5-MAPDB 6-APB 6-APDB 6-Chloro-MDMA 6-EAPB 6-IT 6-MAPB 6-MAPDB EDA IAP 2,3-MDA 3,4-MDA (tenamfetamine) MDEA MDHMA MDMA (midomafetamine) MDOH Methamnetamine MMDMA Naphthylaminopropane TAP Others: 3,4-DCA Amiflamine DiFMDA Selegiline (also D-Deprenyl)
Phentermines	Stimulants: Chlorphentermine Cloforex Clortermine Etolorex Mephentermine Pentorex Phentermine Entactogens: MDPH MDMPH Others: Cericlamine
Cathinones	Stimulants: 3-FMC 4-MC 4-BMC 4-CMC 4-EMC 4-FMC 4-MEC 4-MeMABP 4-MPD Amfepramone Benzedrone Brephedrone Buphedrone Bupropion Cathinone Dimethylcathinone Ethcathinone Eutylone Hydroxybupropion Methcathinone Methedrone NEB N-Ethylhexedrone N-Ethylpentedrone Pentedrone Pentylone Radafaxine Entactogens: 3,4-DMMC 3-MMC Butylone Ethylone Methylone Methylenedioxycathinone Mephedrone
Phenylisobutylamines	Entactogens: 4-CAB 4-MAB Ariadne BDB Butylone EBDB Eutylone MBDB Stimulants: Phenylisobutylamine
Phenylalkylpyrrolidines	Stimulants: α-PBP α-PHP α-PPP α-PVP MDPBP MDPPP MDPV 4-MePBP 4-MePHP 4-MePPP MOPPP MOPVP MPBP MPHP MPPP Naphyrone PEP Prolintane Pyrovalerone
Catecholamines (and close relatives)	6-FNE 6-OHDA a-Me-DA a-Me-TRA Adrenochrome Ciladopa D-DOPA (Dextrodopa) Dimetofrine Dopamine Epinephrine Epinine Etilefrine Ethylnorepinephrine Fenclonine Ibopamine Isoprenaline Isoetarine L-DOPA (Levodopa) L-DOPS (Droxidopa) L-Phenylalanine L-Tyrosine m-Tyramine Metanephrine Metaraminol Metaterol Metirosine Methyldopa N,N-Dimethyldopamine Nordefrin (Levonordefrin) Norepinephrine Norfenefrine (m-Octopamine) Normetanephrine Orciprenaline p-Octopamine p-Tyramine Phenylephrine Synephrine
Miscellaneous	AL-LAD Amidephrine Arbutamine Cafedrine Denopamine Desvenlafaxine Diphenidine Dizocilpine Dobutamine Dopexamine Ephenidine Etafedrine ETH-LAD Famprofazone Fluorolintane Hexapradol IP-LAD Lysergic acid amide Lysergic acid 2-butyl amide Lysergic acid 2,4-dimethylazetidide Lysergic acid diethylamide Methoxamine Methoxphenidine MT-45 PARGY-LAD Phenibut PRO-LAD Pronethalol Salbutamol (Levosalbutamol) Solriamfetol Theodrenaline Thiamphenicol UWA-101 Venlafaxine

Categories:

See also

References