Identification

Name
Carbidopa
Accession Number
DB00190  (APRD00160)
Type
Small Molecule
Groups
Approved
Description

Carbidopa presents a chemical denomination of N-amino-alpha-methyl-3-hydroxy-L-tyrosine monohydrate. It potently inhibits aromatic amino acid decarboxylase (DDC) and due to its chemical properties, it does not cross the blood-brain barrier. Due to its activity, carbidopa is always administered concomitantly with Levodopa. An individual formulation containing solely carbidopa was generated to treat nausea in patients where the combination therapy Levodopa/carbidopa is not efficient reducing nausea.[9]

The first approved product by the FDA containing only carbidopa was developed by Amerigens Pharmaceuticals Ltd and approved on 2014.[10] On the other hand, the combination treatment of carbidopa/levodopa was originally developed by Watson Labs but the historical information by the FDA brings back to the approval of this combination therapy developed by Mayne Pharma in 1992.[F5113]

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
  • Carbidopa
  • Carbidopa (anhydrous)
  • Carbidopa anhydrous
  • 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
LodosynTablet25 mg/1OralAton Pharma, Inc.2010-04-13Not applicableUs
LodosynTablet25 mg/1OralAvera McKennan Hospital2015-11-132018-06-07Us
LodosynTablet25 mg/1OralKaiser Foundations Hospitals2012-09-25Not applicableUs
LodosynTablet25 mg/1OralBristol Myers Squibb Pharma Company2009-06-012013-10-19Us0056 051120180907 15195 a5iyv3
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CarbidopaTablet25 mg/1OralOceanside Pharmaceuticals2014-04-04Not applicableUs
CarbidopaTablet25 mg/1OralZydus Pharmaceuticals (USA) Inc.2018-09-06Not applicableUs
CarbidopaTablet25 mg/1OralNovel Laboratories, Inc.2017-10-20Not applicableUs
CarbidopaTablet25 mg/1OralAmerigen Pharmaceuticals Inc.2014-03-10Not applicableUs
CarbidopaTablet25 mg/1OralCadila Healthcare Limited2018-09-06Not applicableUs
CarbidopaTablet25 mg/1OralLupin Pharmaceuticals2017-10-20Not applicableUs
CarbidopaTablet25 mg/1OralEdenbridge Pharmaceuticals Llc2016-03-02Not applicableUs
CarbidopaTablet25 mg/1OralKAISER FOUNDATION HOSPITALS2017-02-142019-01-31Us
CarbidopaTablet25 mg/1OralIngenus Pharmaceuticals Nj, Llc2016-03-02Not applicableUs
CarbidopaTablet25 mg/1OralTrupharma, Llc2013-11-012014-08-19Us
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 hydrate (25 mg/1) + Levodopa (100 mg/1)TabletOralMylan Pharmaceuticals Inc.2011-05-16Not applicableUs
Carbidopa and LevodopaCarbidopa hydrate (25 mg/1) + Levodopa (100 mg/1)Tablet, extended releaseOralNcs Health Care Of Ky, Inc Dba Vangard Labs2011-10-18Not applicableUs
Carbidopa and LevodopaCarbidopa hydrate (25 mg/1) + Levodopa (100 mg/1)TabletOralGolden State Medical Supply Inc.2018-07-16Not applicableUs
Carbidopa and LevodopaCarbidopa hydrate (50 mg/1) + Levodopa (200 mg/1)Tablet, extended releaseOralAphena Pharma Solutions Tennessee, Inc.1999-10-06Not applicableUs
Carbidopa and LevodopaCarbidopa hydrate (25 mg/1) + Levodopa (100 mg/1)TabletOralMajor2011-05-19Not 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[C@@](CC1=CC(O)=C(O)C=C1)(NN)C(O)=O

Pharmacology

Indication

Carbidopa is indicated with Levodopa for the treatment of symptoms of idiopathic Parkinson disease, postencephalitic parkinsonism and symptomatic parkinsonism followed by carbon monoxide or manganese intoxication.[Label]

The combination therapy is administered for the reduction of Levodopa-driven nausea and vomiting.[Label]

The product of carbidopa should be used in patients where the combination therapy of carbidopa/Levodopa provide less than the adequate daily dosage.[Label]

As well carbidopa can be used in patients where the dosages of carbidopa and Levodopa require individual titration.[Label]

Associated Conditions
Pharmacodynamics

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 an increased amount of Levodopa and Oxitriptan available for transport to the central nervous system. Carbidopa also inhibits the metabolism of Levodopa in the GI tract, thus, increasing the bioavailability of Levodopa.[4]

The presence of additional units of circulating Levodopa can increase the effectiveness of the still functional dopaminergic neurons and it has been shown to alleviate symptoms for a time. The action of carbidopa is very important as Levodopa is able to cross the blood-brain barrier while dopamine cannot.[8] Hence the administration of carbidopa is essential to prevent the transformation of external Levodopa to dopamine before reaching the main action site in the brain.

The coadministration of carbidopa with Levodopa has been shown to increase the half-life of Levodopa more than 1.5 times while increasing the plasma level and decreasing clearance. The combination therapy has also shown an increase of the recovery of Levodopa in urine instead of dopamine which proves a reduced metabolism. This effect has been highly observed by a significant reduction in Levodopa requirements and a significant reduction in the presence of side effects such as nausea. It has been observed that the effect of carbidopa is not dose-dependent.[9]

Mechanism of action

Carbidopa is an inhibitor of the DDC which in order, inhibits the peripheral metabolism of levodopa.[3] DDC is very important in the biosynthesis of L-tryptophan to serotonin and the modification of L-DOPA to dopamine.[4]

DDC can be found in the body periphery and in the blood-brain barrier.[4] The action of carbidopa is focused on peripheral DDC as this drug cannot cross the blood-brain barrier.[8] Hence, it will prevent the metabolism of Levodopa in the periphery but it will not have any activity on the generation of dopamine in the brain.

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

When Levodopa/carbidopa is administered orally, 40-70% of the administered dose is absorbed.[12] Once absorbed, carbidopa shows bioavailability of 58%.[5] A maximum concentration of 0.085 mcg/ml was achieved after 143 min with an AUC of 19.28 mcg.min/ml.[6]

Volume of distribution

The volume of distribution reported for the combination therapy of carbidopa/Levodopa is of 3.6 L/kg.[7] However, carbidopa is widely distributed in the tissues, except in the brain.[12] After one hour, carbidopa is found mainly in the kidney, lungs, small intestine and liver.[1]

Protein binding

It is widely accepted that the protein binding of carbidopa is 76%. However, more studies are required or the presentation of the source of this information.

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).[1]

Route of elimination

In animal studies, 66% of the administered dose of carbidopa was eliminated via the urine while 11% was found in feces. These studies were performed in humans and it was observed a urine excretion covering 50% of the administered dose.[1]

Half life

The reported half-life of carbidopa is of approximately 107 minutes.[6]

Clearance

The reported clearance rate for the combination therapy of Levodopa/carbidopa is 51.7 L/h.[7]

Toxicity

The LD50 of carbidopa is reported to be in the rat of 4810 mg/kg.[MSDS] In animal studies, carbidopa showed no incidences on neoplasia and showed no effect on the fertility status and development.[Label]

No reports of overdosage have been registered with the carbidopa-only product. In the event of overdosage, immediate gastric lavage is recommended as well as intravenous fluid administration. Continuous electrocardiographic monitoring is required.[Label]

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic AcidThe risk or severity of hypotension can be increased when Carbidopa is combined with 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
AbacavirCarbidopa may decrease the excretion rate of Abacavir which could result in a higher serum level.
AcarboseCarbidopa may decrease the excretion rate of Acarbose which could result in a higher serum level.
AcebutololThe risk or severity of hypotension can be increased when Carbidopa is combined with Acebutolol.
AceclofenacAceclofenac may decrease the excretion rate of Carbidopa which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Carbidopa which could result in a higher serum level.
AcetaminophenCarbidopa may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Carbidopa which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Carbidopa which could result in a higher serum level.
AclidiniumCarbidopa may decrease the excretion rate of Aclidinium which could result in a higher serum level.
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]
  3. Mittur A, Gupta S, Modi NB: Pharmacokinetics of Rytary((R)), An Extended-Release Capsule Formulation of Carbidopa-Levodopa. Clin Pharmacokinet. 2017 Sep;56(9):999-1014. doi: 10.1007/s40262-017-0511-y. [PubMed:28236251]
  4. 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]
  5. Yeh KC, August TF, Bush DF, Lasseter KC, Musson DG, Schwartz S, Smith ME, Titus DC: Pharmacokinetics and bioavailability of Sinemet CR: a summary of human studies. Neurology. 1989 Nov;39(11 Suppl 2):25-38. [PubMed:2685649]
  6. Nyholm D, Lewander T, Gomes-Trolin C, Backstrom T, Panagiotidis G, Ehrnebo M, Nystrom C, Aquilonius SM: Pharmacokinetics of levodopa/carbidopa microtablets versus levodopa/benserazide and levodopa/carbidopa in healthy volunteers. Clin Neuropharmacol. 2012 May-Jun;35(3):111-7. doi: 10.1097/WNF.0b013e31825645d1. [PubMed:22549097]
  7. Chana P, Fierro A, Reyes-Parada M, Saez-Briones P: [Pharmacokinetic comparison of Sinemet and Grifoparkin (levodopa/carbidopa 250/25 mg) in Parkinson s disease: a single dose study]. Rev Med Chil. 2003 Jun;131(6):623-31. [PubMed:12942590]
  8. Rang, H. P. and Dale, M. M. (2012). Rang and Dale's Pharmacology (7th ed.). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]
  9. Ahlskog J. (2009). Parkinson's disease treatment guide for physicians. Oxford University Press. [ISBN:978-0-19-537177-2]
  10. FDA approvals [Link]
  11. FDA approvals [Link]
  12. Glown [Link]
External Links
Human Metabolome Database
HMDB0014336
KEGG Drug
D00558
PubChem Compound
34359
PubChem Substance
46508775
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
PDB Entries
1js3
FDA label
Download (280 KB)
MSDS
Download (73.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentParkinson's Disease (PD)1
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
1CompletedTreatmentHigh Blood Pressure (Hypertension)1
1CompletedTreatmentParkinson's Disease (PD)18
1CompletedTreatmentPharmacokinetics1
1CompletedTreatmentSmoking1
1Enrolling by InvitationTreatmentDiabetes Mellitus (DM)1
1RecruitingOtherParkinson's Disease (PD)1
1RecruitingSupportive CareParkinson's Disease (PD)1
1RecruitingTreatmentDisseminated Sclerosis1
1RecruitingTreatmentParkinson's Disease (PD)1
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 Disorder With Hyperactivity (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
2Not Yet RecruitingTreatmentParkinson's Disease (PD)1
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
3Active Not RecruitingTreatmentParkinson's Disease (PD)1
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
3TerminatedTreatmentParkinson's Disease (PD)1
4CompletedTreatmentAdvanced Idiopathic Parkinson's Disease1
4CompletedTreatmentDyskinesias / Parkinson's Disease (PD)1
4CompletedTreatmentIdiopathic Parkinson's Disease1
4CompletedTreatmentImpulse Control Disorder1
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
4RecruitingTreatmentDepression1
4RecruitingTreatmentDepression / Dysthymic Disorder / Major Depressive Disorder (MDD)1
4RecruitingTreatmentObstructive Sleep Apnea (OSA) / Parkinson's Disease (PD)1
4RecruitingTreatmentParkinson's Disease (PD)2
4TerminatedTreatmentParkinson's Disease (PD)1
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 Disease1
Not AvailableRecruitingTreatmentParkinson's Disease (PD) / Sleep disorders and disturbances1

Pharmacoeconomics

Manufacturers
  • Aton pharma inc
Packagers
  • Aton Pharma Inc.
  • Bristol-Myers Squibb Co.
  • Kaiser Foundation Hospital
  • Medisca Inc.
  • Merck & Co.
Dosage forms
FormRouteStrength
TabletOral
TabletOral10 mg/1
Tablet, extended releaseOral25 mg/1
GelEnteral
SuspensionEnteral
TabletOral25 mg/1
Capsule, extended releaseOral
Tablet, orally disintegratingOral
Tablet, extended releaseOral
Tablet, film coatedOral
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)
US6500867No2002-12-312020-06-29Us
US6797732No2004-09-282020-06-29Us
US9089607No2015-07-282028-12-26Us
US8377474No2013-02-192028-12-26Us
US8454998No2013-06-042028-12-26Us
US7094427No2006-08-222022-05-29Us
US8557283No2013-10-152028-12-26Us
US9089608No2015-07-282028-12-26Us
US9463246No2016-10-112028-12-26Us
US9533046No2017-01-032028-12-26Us
US9901640No2018-02-272028-12-26Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)203-208 °C'MSDS'
boiling point (°C)DecomposesChemspider
water solubility3.8 mg/L'MSDS'
logP-1.9Kirk K., Yoshida S., and Haufe G. Fluorine and Health. (2008)
pKa2.3Konduru N. and Madhuri G. (2014). IJPSR. Vol. 5
Predicted Properties
PropertyValueSource
Water Solubility3.73 mg/mLALOGPS
logP-0.16ALOGPS
logP-1.2ChemAxon
logS-1.8ALOGPS
pKa (Strongest Acidic)2.35ChemAxon
pKa (Strongest Basic)5.66ChemAxon
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 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
Humans
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 February 21, 2019 22:32