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Identification
NameCarbidopa
Accession NumberDB00190  (APRD00160)
Typesmall molecule
Groupsapproved
Description

An inhibitor of DOPA decarboxylase, preventing conversion of levodopa to dopamine. It is used in parkinson disease to reduce peripheral adverse effects of levodopa. It has no antiparkinson actions by itself. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
(S)-(−)-carbidopa hydrateNot AvailableNot Available
(S)-carbidopa hydrateNot AvailableNot Available
carbidopa hydrateNot AvailableNot Available
Carbidopa monohydrateNot AvailableNot Available
CarbidopumLatinINN
SaltsNot Available
Brand names
NameCompany
LodosynAton
Brand mixtures
Brand NameIngredients
Apo-Levocarbcarbidopa + levodopa
Apo-Levocarb CR Controlled-Release Tabletscarbidopa + levodopa
Atametcarbidopa + levodopa
Dom-Levo-Carbidopacarbidopa + levodopa
Novo-Levocarbidopacarbidopa + levodopa
Nu-Levocarbcarbidopa + levodopa
Sinemetcarbidopa + levodopa
Sinemet CRcarbidopa + levodopa
Categories
CAS number28860-95-9
WeightAverage: 244.2444
Monoisotopic: 244.105921632
Chemical FormulaC10H16N2O5
InChI KeyInChIKey=QTAOMKOIBXZKND-PPHPATTJSA-N
InChI
InChI=1S/C10H14N2O4.H2O/c1-10(12-11,9(15)16)5-6-2-3-7(13)8(14)4-6;/h2-4,12-14H,5,11H2,1H3,(H,15,16);1H2/t10-;/m0./s1
IUPAC Name
(2S)-3-(3,4-dihydroxyphenyl)-2-hydrazinyl-2-methylpropanoic acid hydrate
SMILES
O.C[C@@](CC1=CC(O)=C(O)C=C1)(NN)C(O)=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassPhenols and Derivatives
Direct parentCatecholamines and Derivatives
Alternative parentsPhenylpropanoic Acids; Alpha Amino Acids and Derivatives; Amphetamines and Derivatives; Amino Fatty Acids; Polyols; Enolates; Carboxylic Acids; Polyamines; Enols; Hydrazines and Derivatives
Substituentspolyol; carboxylic acid; enolate; carboxylic acid derivative; enol; polyamine; hydrazine derivative; amine; organonitrogen compound
Classification descriptionThis compound belongs to the catecholamines and derivatives. These are compounds containing 4-(2-Aminoethyl)pyrocatechol [4-(2-aminoethyl)benzene-1,2-diol] or a derivative thereof formed by substitution.
Pharmacology
IndicationFor treatment of the symptoms of idiopathic Parkinson's disease (paralysis agitans), post-encephalitic parkinsonism
PharmacodynamicsCarbidopa, a noncompetitive decarboxylase inhibitor, is used in combination with levodopa for the treatment of Parkinson's disease.
Mechanism of actionWhen mixed with levodopa, carbidopa inhibits the peripheral conversion of levodopa to dopamine and the decarboxylation of oxitriptan to serotonin by aromatic L-amino acid decarboxylase. This results in increased amount of levodopa and oxitriptan available for transport to the CNS. Carbidopa also inhibits the metabolism of levodopa in the GI tract, thus, increasing the bioavailability of levodopa.
AbsorptionRapidly decarboxylated to dopamine in extracerebral tissues so that only a small portion of a given dose is transported unchanged to the central nervous system.
Volume of distributionNot Available
Protein binding76%
Metabolism

The loss of the hydrazine functional group (probably as molecular nitrogen) represents the major metabolic pathway for carbidopa. There are several metabolites of carbidopa metabolism including 3-(3,4-dihydroxyphenyl)-2-methylpropionic acid, 3-(4-hydroxy-3-methoxyphenyl)-2-methylpropionic acid, 3-(3-hydroxyphenyl)-2-methylpropionic acid, 3-(4-hydroxy-3-methoxyphenyl)-2-methyllactic acid, 3-(3-hydroxyphenyl)-2-methyllactic acid, and 3,4-dihydroxyphenylacetone (1,2). [PMID: 4150141]

SubstrateEnzymesProduct
Carbidopa
    3,4-DihydroxyphenylacetoneDetails
    Carbidopa
      3-(3-hydroxyphenyl)-2-methyllactic acidDetails
      Carbidopa
        3-(3-hydroxyphenyl)-2-methylpropionic acidDetails
        Carbidopa
          3-(3,4-dihydroxyphenyl)-2-methylpropionic acidDetails
          Carbidopa
            3-(4-hydroxy-3-methoxyphenyl)-2-methyllactic acidDetails
            Carbidopa
              3-(4-hydroxy-3-methoxyphenyl)-2-methylpropionic acidDetails
              Route of eliminationIn clinical pharmacologic studies, simultaneous administration of separate tablets of carbidopa and levodopa produced greater urinary excretion of levodopa in proportion to the excretion of dopamine when compared to the two drugs administered at separate times.
              Half life1-2 hours
              ClearanceNot Available
              ToxicitySymptoms of a carbidopa toxicity include muscle spasms or weakness, spasms of the eyelid, nausea, vomiting, diarrhea, an irregular heartbeat, confusion, agitation, hallucinations, and unconsciousness.
              Affected organisms
              • Humans and other mammals
              PathwaysNot Available
              SNP Mediated EffectsNot Available
              SNP Mediated Adverse Drug ReactionsNot Available
              ADMET
              Predicted ADMET features
              Property Value Probability
              Human Intestinal Absorption + 0.8638
              Blood Brain Barrier - 0.9659
              Caco-2 permeable - 0.7517
              P-glycoprotein substrate Substrate 0.5584
              P-glycoprotein inhibitor I Non-inhibitor 0.9619
              P-glycoprotein inhibitor II Non-inhibitor 0.9952
              Renal organic cation transporter Non-inhibitor 0.9484
              CYP450 2C9 substrate Non-substrate 0.7843
              CYP450 2D6 substrate Non-substrate 0.8017
              CYP450 3A4 substrate Non-substrate 0.6267
              CYP450 1A2 substrate Inhibitor 0.9106
              CYP450 2C9 substrate Non-inhibitor 0.9071
              CYP450 2D6 substrate Non-inhibitor 0.9231
              CYP450 2C19 substrate Non-inhibitor 0.9025
              CYP450 3A4 substrate Non-inhibitor 0.8308
              CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9615
              Ames test AMES toxic 0.9107
              Carcinogenicity Non-carcinogens 0.7848
              Biodegradation Not ready biodegradable 0.9741
              Rat acute toxicity 2.0520 LD50, mol/kg Not applicable
              hERG inhibition (predictor I) Weak inhibitor 0.9868
              hERG inhibition (predictor II) Non-inhibitor 0.9413
              Pharmacoeconomics
              Manufacturers
              • Aton pharma inc
              Packagers
              Dosage forms
              FormRouteStrength
              TabletOral
              Prices
              Unit descriptionCostUnit
              Carbidopa powder27.54USDg
              Lodosyn 25 mg tablet2.53USDtablet
              DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
              PatentsNot Available
              Properties
              Statesolid
              Experimental Properties
              PropertyValueSource
              melting point208 °CPhysProp
              water solubility3.8 mg/LNot Available
              logP-1.9Not Available
              Predicted Properties
              PropertyValueSource
              logP-1.2ChemAxon
              pKa (strongest acidic)3.59ChemAxon
              pKa (strongest basic)5.65ChemAxon
              physiological charge-1ChemAxon
              hydrogen acceptor count6ChemAxon
              hydrogen donor count5ChemAxon
              polar surface area115.81ChemAxon
              rotatable bond count4ChemAxon
              refractivity68.77ChemAxon
              polarizability21.81ChemAxon
              number of rings1ChemAxon
              bioavailability1ChemAxon
              rule of fiveYesChemAxon
              Ghose filterNoChemAxon
              Veber's ruleNoChemAxon
              MDDR-like ruleNoChemAxon
              Spectra
              SpectraNot Available
              References
              Synthesis Reference

              Sweta GUPTA, “EXTENDED RELEASE PHARMACEUTICAL DOSAGE FORMS OF CARBIDOPA AND LEVODOPA AND PROCESS OF PREPARATION THEREOF.” U.S. Patent US20130195973, issued August 01, 2013.

              US20130195973
              General Reference
              1. Vickers S, Stuart EK, Bianchine JR, Hucker HB, Jaffe ME, Rhodes RE, Vandenheuvel WJ: Metabolism of carbidopa (1-(-)-alpha-hydrazino-3,4-dihydroxy-alpha-methylhydrocinnamic acid monohydrate), an aromatic amino acid decarboxylase inhibitor, in the rat, rhesus monkey, and man. Drug Metab Dispos. 1974 Jan-Feb;2(1):9-22. Pubmed
              2. Vickers S, Stuart EK, Hucker HB: Further studies on the metabolism of carbidopa, (minus)-L-alpha-hydrazino-3,4-dihydroxy-alpha-methylbenzenepropanoic acid monohydrate, in the human, Rhesus monkey, dog, and rat. J Med Chem. 1975 Feb;18(2):134-8. Pubmed
              External Links
              ResourceLink
              KEGG DrugD00558
              ChEBI3395
              ChEMBLCHEMBL1200748
              Therapeutic Targets DatabaseDAP000592
              PharmGKBPA448794
              RxListhttp://www.rxlist.com/cgi/generic/sinemet.htm
              Drugs.comhttp://www.drugs.com/cdi/carbidopa.html
              WikipediaCarbidopa
              ATC CodesNot Available
              AHFS CodesNot Available
              PDB Entries
              FDA labelNot Available
              MSDSshow(73.4 KB)
              Interactions
              Drug InteractionsSearched, but no interactions found.
              Food InteractionsNot Available

              1. Aromatic-L-amino-acid decarboxylase

              Kind: protein

              Organism: Human

              Pharmacological action: yes

              Actions: inhibitor

              Components

              Name UniProt ID Details
              Aromatic-L-amino-acid decarboxylase P20711 Details

              References:

              1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
              2. Durso R, Evans JE, Josephs E, Szabo G, Evans B, Fernandez HH, Browne TR: Variable absorption of carbidopa affects both peripheral and central levodopa metabolism. J Clin Pharmacol. 2000 Aug;40(8):854-60. Pubmed
              3. Yee RE, Cheng DW, Huang SC, Namavari M, Satyamurthy N, Barrio JR: Blood-brain barrier and neuronal membrane transport of 6-[18F]fluoro-L-DOPA. Biochem Pharmacol. 2001 Nov 15;62(10):1409-15. Pubmed
              4. Kaufmann H, Saadia D, Voustianiouk A, Goldstein DS, Holmes C, Yahr MD, Nardin R, Freeman R: Norepinephrine precursor therapy in neurogenic orthostatic hypotension. Circulation. 2003 Aug 12;108(6):724-8. Epub 2003 Jul 28. Pubmed
              5. Orlefors H, Sundin A, Lu L, Oberg K, Langstrom B, Eriksson B, Bergstrom M: Carbidopa pretreatment improves image interpretation and visualisation of carcinoid tumours with 11C-5-hydroxytryptophan positron emission tomography. Eur J Nucl Med Mol Imaging. 2006 Jan;33(1):60-5. Epub 2005 Sep 24. Pubmed
              6. Calabrese V, Mancuso C, Ravagna A, Perluigi M, Cini C, De Marco C, Butterfield DA, Stella AM: In vivo induction of heat shock proteins in the substantia nigra following L-DOPA administration is associated with increased activity of mitochondrial complex I and nitrosative stress in rats: regulation by glutathione redox state. J Neurochem. 2007 May;101(3):709-17. Epub 2007 Jan 4. Pubmed
              7. Gilbert JA, Frederick LM, Ames MM: The aromatic-L-amino acid decarboxylase inhibitor carbidopa is selectively cytotoxic to human pulmonary carcinoid and small cell lung carcinoma cells. Clin Cancer Res. 2000 Nov;6(11):4365-72. Pubmed

              Comments
              Drug created on June 13, 2005 07:24 / Updated on September 24, 2013 16:39