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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
ParcopaCarbidopa + L-DOPA
Sinemetcarbidopa + levodopa
Sinemet CRcarbidopa + levodopa
Categories
CAS number28860-95-9
WeightAverage: 244.2444
Monoisotopic: 244.105921632
Chemical FormulaC10H16N2O5
InChI KeyQTAOMKOIBXZKND-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
Not Available
3,4-DihydroxyphenylacetoneDetails
Carbidopa
Not Available
3-(3-hydroxyphenyl)-2-methyllactic acidDetails
Carbidopa
Not Available
3-(3-hydroxyphenyl)-2-methylpropionic acidDetails
Carbidopa
Not Available
3-(3,4-dihydroxyphenyl)-2-methylpropionic acidDetails
Carbidopa
Not Available
3-(4-hydroxy-3-methoxyphenyl)-2-methyllactic acidDetails
Carbidopa
Not Available
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

Targets

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

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