Identification

Name
Carbidopa
Accession Number
DB00190  (APRD00160)
Type
Small Molecule
Groups
Approved
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
  • (-)-L-alpha-Hydrazino-3,4-dihydroxy-alpha-methylhydrocinnamic acid monohydrate
  • (S)-(−)-carbidopa
  • (S)-carbidopa
  • (αS)-α-hydrazino-3,4-dihydroxy-α-methylbenzenepropanoic acid
  • Carbidopum
  • L-3-(3,4-dihydroxyphenyl)-2-methyl-2-hydrazinopropionic acid
  • L-α-methyldopahydrazine
External IDs
MK-486
Product Ingredients
IngredientUNIICASInChI Key
Carbidopa hydrateMNX7R8C5VO38821-49-7QTAOMKOIBXZKND-PPHPATTJSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CarbidopaTablet25 mg/1OralKaiser Foundations Hospitals2017-02-14Not applicableUs
CarbidopaTablet25 mg/1OralOceanside Pharmaceuticals2014-04-04Not applicableUs
LodosynTablet25 mg/1OralKaiser Foundations Hospitals2012-09-25Not applicableUs
LodosynTablet25 mg/1OralAvera Mc Kennan Hospital2015-11-13Not applicableUs
LodosynTablet25 mg/1OralAton Pharma, Inc.2010-04-13Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CarbidopaTablet25 mg/1OralAmerigen Pharmaceuticals Inc.2013-11-01Not applicableUs
CarbidopaTablet25 mg/1OralIngenus Pharmaceuticals Nj, Llc2016-03-02Not applicableUs
CarbidopaTablet25 mg/1OralEdenbridge Pharmaceuticals Llc2016-03-02Not applicableUs
Carbidopa and LevodopaTablet25 mg/1OralRemedy Repack2013-02-272016-10-18Us
Carbidopa and levodopaTablet25 mg/1OralRemedy Repack2013-03-252017-02-22Us
Carbidopa Tablets, 25 mgTablet25 mg/1OralAlvogen, Inc.2016-01-26Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Apo-levocarb - Tab 10mg/100mgCarbidopa (10 mg) + Levodopa (100 mg)TabletOralApotex Corporation1995-12-31Not applicableCanada
Apo-levocarb - Tab 25mg/250mgCarbidopa (25 mg) + Levodopa (250 mg)TabletOralApotex Corporation1995-12-31Not applicableCanada
Apo-levocarb CRCarbidopa (50 mg) + Levodopa (200 mg)Tablet, extended releaseOralApotex Corporation2003-11-13Not applicableCanada
Apo-levocarb CRCarbidopa (25 mg) + Levodopa (100 mg)Tablet, extended releaseOralApotex Corporation2009-02-04Not applicableCanada
Apo-levocarb-tab 25mg/100mgCarbidopa (25 mg) + Levodopa (100 mg)TabletOralApotex Corporation1995-12-31Not applicableCanada
Carbidopa and LevodopaCarbidopa (25 mg/1) + Levodopa (100 mg/1)TabletOralNu Care Pharmaceuticals,inc.2008-10-28Not applicableUs
Carbidopa and levodopaCarbidopa (25 mg/1) + Levodopa (100 mg/1)TabletOralAphena Pharma Solutions Tennessee, Inc.1993-09-01Not applicableUs
Carbidopa and LevodopaCarbidopa (10 mg/1) + Levodopa (100 mg/1)TabletOralCardinal Health2011-05-19Not applicableUs
Carbidopa and LevodopaCarbidopa (25 mg/1) + Levodopa (100 mg/1)Tablet, extended releaseOralAmerincan Health Packaging2015-10-012017-02-09Us
Carbidopa and LevodopaCarbidopa (25 mg/1) + Levodopa (100 mg/1)TabletOralMylan Pharmaceuticals2011-05-16Not applicableUs
Categories
UNII
KR87B45RGH
CAS number
28860-95-9
Weight
Average: 226.2292
Monoisotopic: 226.095356946
Chemical Formula
C10H14N2O4
InChI Key
TZFNLOMSOLWIDK-JTQLQIEISA-N
InChI
InChI=1S/C10H14N2O4/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)/t10-/m0/s1
IUPAC Name
(2S)-3-(3,4-dihydroxyphenyl)-2-hydrazinyl-2-methylpropanoic acid
SMILES
C[[email protected]@](CC1=CC(O)=C(O)C=C1)(NN)C(O)=O

Pharmacology

Indication

For treatment of the symptoms of idiopathic Parkinson's disease (paralysis agitans), post-encephalitic parkinsonism

Structured Indications
Pharmacodynamics

Carbidopa, a noncompetitive decarboxylase inhibitor, is used in combination with levodopa for the treatment of Parkinson's disease.

Mechanism of action

When 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.

TargetActionsOrganism
AAromatic-L-amino-acid decarboxylase
inhibitor
Human
Absorption

Rapidly 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 distribution
Not Available
Protein binding

76%

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]

Route of elimination

In 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 life

1-2 hours

Clearance
Not Available
Toxicity

Symptoms 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
DroxidopaThe therapeutic efficacy of Droxidopa can be decreased when used in combination with Carbidopa.Approved, Investigational
Food Interactions
Not 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 References
  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:4150141]
  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:804550]
External Links
KEGG Drug
D00558
ChemSpider
31640
BindingDB
50418773
ChEBI
39585
ChEMBL
CHEMBL1201236
Therapeutic Targets Database
DAP000592
PharmGKB
PA448794
HET
142
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Carbidopa
AHFS Codes
  • 28:36.12 — Catechol-o-methyltransferase (Comt) Inhibitors
  • 28:36.16 — Dopamine Precursors
PDB Entries
1js3
MSDS
Download (73.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableAutonomic Failure / Idiopathic orthostatic hypotension1
1CompletedNot AvailableHealthy Volunteers2
1CompletedNot AvailableParkinson's Disease (PD)1
1CompletedBasic ScienceCocaine Abuse1
1CompletedTreatmentAngelman's syndrome1
1CompletedTreatmentAsthma Bronchial1
1CompletedTreatmentHealthy Volunteers5
1CompletedTreatmentHypertensive1
1CompletedTreatmentParkinson's Disease (PD)18
1CompletedTreatmentPharmacokinetics1
1CompletedTreatmentSmoking1
1Enrolling by InvitationTreatmentDiabetes1
1Not Yet RecruitingTreatmentDisseminated Sclerosis1
1, 2CompletedTreatmentParkinson's Disease (PD)3
1, 2TerminatedTreatmentAutonomic Nervous System Diseases / Multiple System Atrophy (MSA) / Parkinson's Disease (PD)1
1, 2Unknown StatusNot AvailableParkinson's Disease (PD)1
2Active Not RecruitingTreatmentParkinson's Disease (PD)1
2CompletedPreventionParkinson's Disease (PD)2
2CompletedTreatmentAdvanced Parkinson's Disease1
2CompletedTreatmentAmblyopia1
2CompletedTreatmentAttention Deficit Hyperactivity Disorder (ADHD)1
2CompletedTreatmentCocaine Abuse / Cocaine-Related Disorders1
2CompletedTreatmentDependence, Cocaine3
2CompletedTreatmentFibromyalgia1
2CompletedTreatmentIdiopathic Parkinson's Disease1
2CompletedTreatmentMotor Fluctuations / Parkinson's Disease (PD)1
2CompletedTreatmentParkinson's Disease (PD)11
2CompletedTreatmentSchizophrenic Disorders1
2RecruitingTreatmentAge-Related Macular Degeneration (ARMD)1
2RecruitingTreatmentAlbinism / Albinism, Oculocutaneous1
2RecruitingTreatmentBaroreflex Failure Syndrome / Familial Dysautonomia1
2RecruitingTreatmentParkinson's Disease (PD)1
2TerminatedTreatmentParkinson´s Disease1
2Unknown StatusTreatmentCocaine Abuse / Cocaine-Related Disorders1
2WithdrawnTreatmentPain, Acute1
2WithdrawnTreatmentParkinson's Disease (PD)1
2, 3Active Not RecruitingOtherOrthostatic Intolerance / Postural Tachycardia Syndrome1
2, 3CompletedTreatmentAngelman's syndrome1
2, 3CompletedTreatmentNonfluent Aphasia / Strokes1
3CompletedNot AvailableParkinson's Disease (PD)2
3CompletedPreventionParkinson's Disease (PD)1
3CompletedTreatmentAdvanced Parkinson's Disease1
3CompletedTreatmentAmblyopia1
3CompletedTreatmentFamilial Dysautonomia1
3CompletedTreatmentParkinson's Disease (PD)4
3Enrolling by InvitationTreatmentAutonomic Nervous System Diseases / Dopamine Beta-Hydroxylase Deficiency / Idiopathic orthostatic hypotension / Orthostatic Intolerance1
3RecruitingTreatmentParkinson's Disease (PD)2
4CompletedTreatmentAdvanced Idiopathic Parkinson's Disease1
4CompletedTreatmentDyskinesias / Parkinson's Disease (PD)1
4CompletedTreatmentIdiopathic Parkinson's Disease1
4CompletedTreatmentParkinson's Disease (PD)6
4CompletedTreatmentParkinson's Disease With End of Dose "Wearing Off" / Parkinson's Disease With End of Dose Wearing Off1
4CompletedTreatmentSub-acute Back Pain1
4RecruitingTreatmentDepressive State1
4RecruitingTreatmentParkinson's Disease (PD)2
4TerminatedTreatmentParkinson's Disease (PD)1
4Unknown StatusTreatmentImpulse Control Disorder1
4WithdrawnTreatmentParkinson's Disease (PD)1
4WithdrawnTreatmentStrokes1
Not AvailableCompletedNot AvailableParkinson's Disease (PD)1
Not AvailableCompletedBasic ScienceDopamine Activity / Episodic Memory Consolidation / Response Preparation1
Not AvailableCompletedDiagnosticParkinson's Disease (PD) / Parkinsonian Syndromes1
Not AvailableCompletedTreatmentIdiopathic Parkinson's Disease1
Not AvailableCompletedTreatmentStrokes1
Not AvailableEnrolling by InvitationTreatmentAngelman's syndrome1
Not AvailableRecruitingNot AvailableAlcohol Dependence / Cocaine Abuse / Dependence, Cocaine / Opiate Dependence / Substance Abuse1
Not AvailableRecruitingNot AvailableAtypical Parkinson Disease / Corticobasal Degeneration / Gait, Frontal / Multiple System Atrophy (MSA) / Parkinson's Disease (PD) / Parkinsonian Disorders / Progressive Supranuclear Palsy (PSP)1
Not AvailableRecruitingNot AvailableParkinson's Disease (PD)1
Not AvailableRecruitingNot AvailableParkinson´s Disease1
Not AvailableRecruitingTreatmentParkinson's Disease (PD) / Sleep disorders and disturbances1

Pharmacoeconomics

Manufacturers
  • Aton pharma inc
Packagers
Dosage forms
FormRouteStrength
Tablet, film coatedOral
GelEnteral
SuspensionEnteral
TabletOral25 mg/1
Tablet, orally disintegratingOral
Capsule, extended releaseOral
TabletOral
Tablet, extended releaseOral
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.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6500867No2000-06-292020-06-29Us
US6797732No2000-06-292020-06-29Us
US9089607No2008-12-262028-12-26Us
US8377474No2008-12-262028-12-26Us
US8454998No2008-12-262028-12-26Us
US7094427No2002-05-292022-05-29Us
US8557283No2008-12-262028-12-26Us
US9089608No2008-12-262028-12-26Us
US9463246No2008-12-262028-12-26Us
US9533046No2008-12-262028-12-26Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)208 °CPhysProp
water solubility3.8 mg/LNot Available
logP-1.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility3.73 mg/mLALOGPS
logP-0.16ALOGPS
logP-1.2ChemAxon
logS-1.8ALOGPS
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
Polarizability22.03 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-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
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenylpropanoic acids. These are compounds with a structure containing a benzene ring conjugated to a propanoic acid.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Phenylpropanoic acids
Sub Class
Not Available
Direct Parent
Phenylpropanoic acids
Alternative Parents
Amphetamines and derivatives / Alpha amino acids and derivatives / Phenylpropanes / Catechols / 1-hydroxy-4-unsubstituted benzenoids / 1-hydroxy-2-unsubstituted benzenoids / Monocarboxylic acids and derivatives / Carboxylic acids / Alkylhydrazines / Organopnictogen compounds
show 3 more
Substituents
3-phenylpropanoic-acid / Alpha-amino acid or derivatives / Amphetamine or derivatives / Phenylpropane / Catechol / 1-hydroxy-4-unsubstituted benzenoid / 1-hydroxy-2-unsubstituted benzenoid / Phenol / Monocyclic benzene moiety / Benzenoid
show 14 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
monocarboxylic acid, catechols, hydrazines (CHEBI:39585)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Pyridoxal phosphate binding
Specific Function
Catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine (DOPA) to dopamine, L-5-hydroxytryptophan to serotonin and L-tryptophan to tryptamine.
Gene Name
DDC
Uniprot ID
P20711
Uniprot Name
Aromatic-L-amino-acid decarboxylase
Molecular Weight
53925.815 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  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:10934669]
  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:11709201]
  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:12885750]
  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:16184369]
  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:17241115]
  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:11106255]

Drug created on June 13, 2005 07:24 / Updated on October 21, 2017 19:20