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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
(-)-L-alpha-Hydrazino-3,4-dihydroxy-alpha-methylhydrocinnamic acid monohydrateNot AvailableNot Available
(2S)-3-(3,4-Dihydroxyphenyl)-2-hydrazinyl-2-methylpropanoic acid hydrateNot AvailableNot Available
(2S)-3-(3,4-Dihydroxyphenyl)-2-hydrazinyl-2-methylpropanoic acid monohydrateNot AvailableNot Available
(AlphaS)-alpha-hydrazino-3,4-dihydroxy-alpha-methylbenzenepropanoic acid monohydrateNot AvailableNot Available
(S)-(-)-Carbidopa hydrateNot AvailableNot Available
(S)-(−)-carbidopa hydrateNot AvailableNot Available
(S)-carbidopa hydrateNot AvailableNot Available
carbidopa hydrateNot AvailableNot Available
Carbidopa monohydrateNot AvailableNot Available
CarbidopumLatinINN
Carbidopum monohydricumNot AvailableNot Available
L-alpha-(3,4-Dihydroxybenzyl)-alpha-hydrazinopropionic acid monohydrateNot AvailableNot Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Lodosyntablet25 mgoralKAISER FOUNDATION HOSPITALS2012-09-25Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Lodosyntablet25 mgoralAton Pharma, Inc2010-04-13Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Carbidopatablet25 mgoralOceanside Pharmaceuticals2014-04-04Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Carbidopatablet25 mgoralAmerigen Pharmaceuticals Inc.2013-11-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Over the Counter ProductsNot Available
International BrandsNot Available
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
SaltsNot Available
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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as 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.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenols and derivatives
Direct ParentCatecholamines and derivatives
Alternative Parents
Substituents
  • 3-phenylpropanoic-acid
  • Catecholamine
  • Amphetamine or derivatives
  • Alpha-amino acid or derivatives
  • N-substituted-alpha-amino acid
  • Phenylpropane
  • Amino fatty acid
  • Fatty acyl
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Hydrazine derivative
  • Carbonyl group
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
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
PropertyValueProbability
Human Intestinal Absorption+0.8638
Blood Brain Barrier-0.9659
Caco-2 permeable-0.7517
P-glycoprotein substrateSubstrate0.5584
P-glycoprotein inhibitor INon-inhibitor0.9619
P-glycoprotein inhibitor IINon-inhibitor0.9952
Renal organic cation transporterNon-inhibitor0.9484
CYP450 2C9 substrateNon-substrate0.7843
CYP450 2D6 substrateNon-substrate0.8017
CYP450 3A4 substrateNon-substrate0.6267
CYP450 1A2 substrateInhibitor0.9106
CYP450 2C9 substrateNon-inhibitor0.9071
CYP450 2D6 substrateNon-inhibitor0.9231
CYP450 2C19 substrateNon-inhibitor0.9025
CYP450 3A4 substrateNon-inhibitor0.8308
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9615
Ames testAMES toxic0.9107
CarcinogenicityNon-carcinogens0.7848
BiodegradationNot ready biodegradable0.9741
Rat acute toxicity2.0520 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9868
hERG inhibition (predictor II)Non-inhibitor0.9413
Pharmacoeconomics
Manufacturers
  • Aton pharma inc
Packagers
Dosage forms
FormRouteStrength
Tabletoral25 mg
Prices
Unit descriptionCostUnit
Carbidopa powder27.54USD g
Lodosyn 25 mg tablet2.53USD tablet
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 Area115.81 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity68.77 m3·mol-1ChemAxon
Polarizability21.81 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
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
ATC CodesNot Available
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSDownload (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