| Version |
2.5 |
| Creation Date |
2005-06-13 13:24:05 |
| Update Date |
2009-02-19 16:24:53 |
| Primary Accession Number |
DB00190 |
| Secondary Accession Number |
|
| Name |
Carbidopa |
| Drug Type |
|
| 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] |
| Synonyms |
- Alpha-Methyldopahydrazine
- C-DOPA
- Carbidopa Anhydrous
- Carbidopa Monohydrate
- Carbidopum [INN-Latin]
- MK-486
- N-Aminomethyldopa
|
| Brand Names |
- Atamet
- HMD
- Lodosin
- Lodosyn
|
| Brand Mixtures |
- Apo-Levocarb (carbidopa + levodopa)
- Apo-Levocarb CR Controlled-Release Tablets (carbidopa + levodopa)
- Atamet (carbidopa + levodopa)
- Dom-Levo-Carbidopa (carbidopa + levodopa)
- Novo-Levocarbidopa (carbidopa + levodopa)
- Nu-Levocarb (carbidopa + levodopa)
- Sinemet (carbidopa + levodopa)
- Sinemet CR (carbidopa + levodopa)
|
| Chemical IUPAC Name |
(2S)-3-(3,4-dihydroxyphenyl)-2-hydrazinyl-2-methylpropanoic acid |
| Chemical Formula |
C10H14N2O4 |
| Chemical Structure |
 |
| CAS Registry Number |
28860-95-9 |
| InChI Identifier |
InChI=1/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/f/h15H |
| InChI Key |
TZFNLOMSOLWIDK-GEPYNMGZDS |
| KEGG Drug |
D00558  |
| KEGG Compound |
Not Available |
| PubChem Compound |
34359  |
| PubChem Substance |
176096  |
| ChEBI ID |
Not Available |
| PharmGKB ID |
PA448794  |
| HET ID |
Not Available |
| GenBank ID |
Not Available |
| Drug ID Number [DIN] |
Not Available |
| RxList Link |
http://www.rxlist.com/cgi/generic/sinemet.htm  |
| PDRhealth Link |
Not Available |
| Wikipedia Link |
http://en.wikipedia.org/wiki/Carbidopa  |
| FDA Label |
Not Available |
| Material Safety Data Sheet (MSDS) |
|
| Synthesis Reference |
Chemerda et al., U.S. Pat. 3,462,536 (1963) |
| Average Molecular Weight |
226.2292 |
| Monoisotopic Molecular Weight |
226.0954 |
| State |
Solid |
| Melting Point |
203-205oC |
| Experimental Water Solubility |
3.8 mg/L
Source: PhysProp
|
| Predicted Water Solubility |
3.73e+00 mg/mL
Calculated using ALOGPS
|
| Experimental LogP/Hydrophobicity |
-1.9
Source: PhysProp
|
| Predicted LogP |
-0.16
Calculated using ALOGPS
|
| Experimental LogS |
Not Available |
| Predicted LogS |
-1.78
Calculated using ALOGPS
|
| Experimental Caco2 Permeability |
Not Available |
| pKa/Isoelectric Point |
Not Available |
| Mass Spectrum |
Not Available
|
| MOL File |
Show | Download  |
| SDF File |
Show | Download  |
| PDB File |
Show | Download  |
| 2D Structure |
|
| 3D Structure |
|
| Experimental PDB ID |
1JS3  |
| Experimental PDB File |
Show |
| Experimental PDB Structure |
|
| Isomeric SMILES |
C[C@@](CC1=CC(O)=C(O)C=C1)(NN)C(O)=O |
| Canonical SMILES |
CC(CC1=CC(O)=C(O)C=C1)(NN)C(O)=O |
| Drug Category |
- Antidyskinetics
- Antiparkinson Agents
- Dopamine Agents
- Enzyme Inhibitors
|
| ATC Codes |
Not Available |
| AHFS Codes |
Not Available |
| Indication |
For treatment of the symptoms of idiopathic Parkinson's disease (paralysis agitans), post-encephalitic parkinsonism |
| Pharmacology |
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. |
| 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. |
| 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. |
| Protein Binding |
76% |
| Biotransformation |
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] |
| Half Life |
1-2 hours |
| Dosage Forms |
|
| Patient Information |
Show  |
| Contraindications |
Show  |
| Interactions |
Show  |
| Drug Interactions |
Not Available
|
| Food Interactions |
Not Available
|
| Pathways |
Not Available
|
| General References |
- 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
]
- 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
]
- Wikipedia

- RxList

|
| Organisms Affected |
|
| Phase 1 Metabolizing Enzymes |
- Catechol O-methyltransferase (COMT)
- Monoamine oxidase type A (MAO-A)
- Monoamine oxidase type B (MAO-B)
|
| Targets |
- Aromatic-L-amino-acid decarboxylase
|
|
Drug Target 1
[top]
|
| Target 1 ID |
3876 |
| Target 1 Name |
Aromatic-L-amino-acid decarboxylase |
| Target 1 Synonyms |
- AADC
- DDC
- DOPA decarboxylase
- EC 4.1.1.28
|
| Target 1 Gene Name |
DDC |
| Target 1 Protein Sequence |
>Aromatic-L-amino-acid decarboxylase
MNASEFRRRGKEMVDYVANYMEGIEGRQVYPDVEPGYLRPLIPAAAPQEPDTFEDIINDV
EKIIMPGVTHWHSPYFFAYFPTASSYPAMLADMLCGAIGCIGFSWAASPACTELETVMMD
WLGKMLELPKAFLNEKAGEGGGVIQGSASEATLVALLAARTKVIHRLQAASPELTQAAIM
EKLVAYSSDQAHSSVERAGLIGGVKLKAIPSDGNFAMRASALQEALERDKAAGLIPFFMV
ATLGTTTCCSFDNLLEVGPICNKEDIWLHVDAAYAGSAFICPEFRHLLNGVEFADSFNFN
PHKWLLVNFDCSAMWVKKRTDLTGAFRLDPTYLKHSHQDSGLITDYRHWQIPLGRRFRSL
KMWFVFRMYGVKGLQAYIRKHVQLSHEFESLVRQDPRFEICVEVILGLVCFRLKGSNKVN
EALLQRINSAKKIHLVPCHLRDKFVLRFAICSRTVESAHVQRAWEHIKELAADVLRAERE
|
| Target 1 Number of Residues |
488 |
| Target 1 Molecular Weight |
53895 |
| Target 1 Theoretical pI |
7.21 |
| Target 1 GO Classification |
|
Function
|
catalytic activity
lyase activity
carbon-carbon lyase activity
carboxy-lyase activity |
|
Process
|
amino acid metabolism
physiological process
metabolism
cellular metabolism
amino acid and derivative metabolism |
|
Component
|
| Not Available |
|
| Target 1 General Function |
Amino acid transport and metabolism |
| Target 1 Specific Function |
Catalyzes the decarboxylation of L-3,4- dihydroxyphenylalanine (DOPA) to dopamine, L-5-hydroxytryptophan to serotonin and L-tryptophan to tryptamine |
| Target 1 Pathways |
| Name |
SMPDB Link |
KEGG Link |
| Alkaloid biosynthesis I |
|
map00340  |
|
| Target 1 Reactions |
- (1) 3,4-dihydroxy-L-phenylalanine = dopamine + CO2
|
| Target 1 Pfam Domain Function |
|
| Target 1 Signals |
|
| Target 1 Transmembrane Regions |
|
| Target 1 Essentiality |
Non-Essential |
| Target 1 GenBank ID Protein |
181521  |
| Target 1 UniProtKB/Swiss-Prot ID |
P20711  |
| Target 1 UniProtKB/Swiss-Prot Entry Name |
DDC_HUMAN  |
| Target 1 PDB ID |
1JS3  |
| Target 1 PDB File |
Show |
| Target 1 3D Structure |
|
| Target 1 Cellular Location |
Not Available |
| Target 1 Gene Sequence |
>1443 bp
ATGAACGCAAGTGAATTCCGAAGGAGAGGGAAGGAGATGGTGGATTACGTGGCCAACTAC
ATGGAAGGCATTGAGGGACGCCAGGTCTACCCTGACGTGGAGCCCGGGTACCTGCGGCCG
CTGATCCCTGCCGCTGCCCCTCAGGAGCCAGACACGTTTGAGGACATCATCAACGACGTT
GAGAAGATAATCATGCCTGGGGTGACGCACTGGCACAGCCCCTACTTCTTCGCCTACTTC
CCCACTGCCAGCTCGTACCCGGCCATGCTTGCGGACATGCTGTGCGGGGCCATTGGCTGC
ATCGGCTTCTCCTGGGCGGCAAGCCCAGCATGCACAGAGCTGGAGACTGTGATGATGGAC
TGGCTCGGGAAGATGCTGGAACTACCAAAGGCATTTTTGAATGAGAAAGCTGGAGAAGGG
GGAGGAGTGATCCAGGGAAGTGCCAGTGAAGCCACCCTGGTGGCCCTGCTGGCCGCTCGG
ACCAAAGTGATCCATCGGCTGCAGGCAGCGTCCCCAGAGCTCACACAGGCCGCTATCATG
GAGAAGCTGGTGGCTTACTCATCCGATCAGGCACACTCCTCAGTGGAAAGAGCTGGGTTA
ATTGGTGGAGTGAAATTAAAAGCCATCCCCTCAGATGGCAACTTCGCCATGCGTGCGTCT
GCCCTGCAGGAAGCCCTGGAGAGAGACAAAGCGGCTGGCCTGATTCCTTTCTTTATGGTT
GCCACCCTGGGGACCACAACATGCTGCTCCTTTGACAATCTCTTAGAAGTCGGTCCTATC
TGCAACAAGGAAGACATATGGCTGCACGTTGATGCAGCCTACGCAGGCAGTGCATTCATC
TGCCCTGAGTTCCGGCACCTTCTGAATGGAGTGGAGTTTGCAGATTCATTCAACTTTAAT
CCCCACAAATGGCTATTGGTGAATTTTGACTGTTCTGCCATGTGGGTGAAAAAGAGAACA
GACTTAACGGGAGCCTTTAGACTGGACCCCACTTACCTGAAGCACAGCCATCAGGATTCA
GGGCTTATCACTGACTACCGGCATTGGCAGATACCACTGGGCAGAAGATTTCGCTCTTTG
AAAATGTGGTTTGTATTTAGGATGTATGGAGTCAAAGGACTGCAGGCTTATATCCGCAAG
CATGTCCAGCTGTCCCATGAGTTTGAGTCACTGGTGCGCCAGGATCCCCGCTTTGAAATC
TGTGTGGAAGTCATTCTGGGGCTTGTCTGCTTTCGGCTAAAGGGTTCCAACAAAGTGAAT
GAAGCTCTTCTGCAAAGAATAAACAGTGCCAAAAAAATCCACTTGGTTCCATGTCACCTC
AGGGACAAGTTTGTCCTGCGCTTTGCCATCTGTTCTCGCACGGTGGAATCTGCCCATGTG
CAGCGGGCCTGGGAACACATCAAAGAGCTGGCGGCCGACGTGCTGCGAGCAGAGAGGGAG
TAG
|
| Target 1 GenBank Gene ID |
|
| Target 1 GeneCard ID |
DDC  |
| Target 1 GenAtlas ID |
DDC  |
| Target 1 HGNC ID |
HGNC:2719  |
| Target 1 Chromosome Location |
7 |
| Target 1 Locus |
7p11 |
| Target 1 SNPs |
SNPJam Report  |
| Target 1 General References |
- Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [PubMed
]
- Craig SP, Thai AL, Weber M, Craig IW: Localisation of the gene for human aromatic L-amino acid decarboxylase (DDC) to chromosome 7p13-->p11 by in situ hybridisation. Cytogenet Cell Genet. 1992;61(2):114-6. [PubMed
]
- Sumi-Ichinose C, Ichinose H, Takahashi E, Hori T, Nagatsu T: Molecular cloning of genomic DNA and chromosomal assignment of the gene for human aromatic L-amino acid decarboxylase, the enzyme for catecholamine and serotonin biosynthesis. Biochemistry. 1992 Mar 3;31(8):2229-38. [PubMed
]
- Scherer LJ, McPherson JD, Wasmuth JJ, Marsh JL: Human dopa decarboxylase: localization to human chromosome 7p11 and characterization of hepatic cDNAs. Genomics. 1992 Jun;13(2):469-71. [PubMed
]
- Ichinose H, Kurosawa Y, Titani K, Fujita K, Nagatsu T: Isolation and characterization of a cDNA clone encoding human aromatic L-amino acid decarboxylase. Biochem Biophys Res Commun. 1989 Nov 15;164(3):1024-30. [PubMed
]
- Le Van Thai A, Coste E, Allen JM, Palmiter RD, Weber MJ: Identification of a neuron-specific promoter of human aromatic L-amino acid decarboxylase gene. Brain Res Mol Brain Res. 1993 Mar;17(3-4):227-38. [PubMed
]
|
| Target 1 Drug References |
- 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
]
- 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
]
- 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
]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed
]
- 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
]
- 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
]
- 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
]
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