DT-Web

DB00190 - Carbidopa


Identification
Name Carbidopa
Accession Number DB00190 (APRD00160)
Type small molecule
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
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 244.2444
Groups approved
Monoisotopic Weight 244.105921632
Pharmacology
Indication For treatment of the symptoms of idiopathic Parkinson's disease (paralysis agitans), post-encephalitic parkinsonism
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.
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]
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.
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
Interactions
Drug Interactions Not Available
Food Interactions Not Available

Targets


Aromatic-L-amino-acid decarboxylase
Name Aromatic-L-amino-acid decarboxylase
Gene Name DDC
Pharmacological action yes
Actions inhibitor
References
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
  • 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
  • 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
  • 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
  • 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
DTHybrid score 0.3553

Predictions


Id Partner name Gene Name Score
807 D-alanine--D-alanine ligase A ddlA 0.0692
894 Alanine racemase alr 0.0691
2453 Alanine racemase alr 0.0691
831 D(2) dopamine receptor DRD2 0.0325
6151 Monocarboxylate transporter 10 SLC16A10 0.0288
4063 Tryptophanyl-tRNA synthetase, mitochondrial WARS2 0.0238
90 Tryptophan 5-hydroxylase 2 TPH2 0.0238
23 D(1A) dopamine receptor DRD1 0.0228
694 Matrix protein 2 M 0.0226
765 Indoleamine 2,3-dioxygenase IDO1 0.0198
556 Alpha-1A adrenergic receptor ADRA1A 0.0195
252 Tryptophanyl-tRNA synthetase, cytoplasmic WARS 0.0186
1588 Multidrug resistance protein 1 ABCB1 0.0179
134 Tryptophan 5-hydroxylase 1 TPH1 0.0175
6012 Tryptophan 2,3-dioxygenase TDO2 0.0173
2452 Tryptophanyl-tRNA synthetase trpS 0.0173
199 Monocarboxylate transporter 8 SLC16A2 0.0153
866 Large neutral amino acids transporter small subunit 2 SLC7A8 0.0149
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.0146
245 Large neutral amino acids transporter small subunit 1 SLC7A5 0.0136
3939 Amine oxidase [flavin-containing] B MAOB 0.0132
502 5-hydroxytryptamine 2A receptor HTR2A 0.013
103 Muscarinic acetylcholine receptor M1 CHRM1 0.0126
6144 Solute carrier family 22 member 2 SLC22A2 0.0115
1517 Beta-3 adrenergic receptor ADRB3 0.0111
6145 Solute carrier family 22 member 1 SLC22A1 0.011
828 Phenylalanine-4-hydroxylase PAH 0.0109
3109 Phenylalanine-4-hydroxylase phhA 0.0109
163 D(1B) dopamine receptor DRD5 0.0109
432 D(4) dopamine receptor DRD4 0.0102
638 D(3) dopamine receptor DRD3 0.0099
1539 Oligopeptide transporter, small intestine isoform SLC15A1 0.0086
789 Alpha-1D adrenergic receptor ADRA1D 0.0086
378 Alpha-2C adrenergic receptor ADRA2C 0.0083
629 Alpha-2B adrenergic receptor ADRA2B 0.0082
193 Beta-1 adrenergic receptor ADRB1 0.0079
766 Beta-2 adrenergic receptor ADRB2 0.0077
632 Alpha-1B adrenergic receptor ADRA1B 0.0077
540 Sodium-dependent noradrenaline transporter SLC6A2 0.0076
318 Alpha-2A adrenergic receptor ADRA2A 0.0073
4119 Cytochrome P450 2D6 CYP2D6 0.0061
3893 DDC protein DDC 0.0038
3891 Putative L-Dopa decarboxylase DDC 0.0037
3908 P-selectin cytoplasmic tail-associated protein pcap 0.0031
3896 CDNA FLJ46802 fis, clone TRACH3032150, moderately similar to Cysteine sulfinic acid decarboxylase GADL1 0.0031
3911 Uncharacterized protein C20orf38 SPTLC3 0.0031
3906 Serine dehydratase-like SDSL 0.0031
3881 Selenocysteine lyase variant Not Available 0.0031
3887 Phosphorylase PYGB 0.0031
3915 Cysteine sulfinic acid decarboxylase-related protein 1 CSAD 0.0031
3914 Alanine-glyoxylate aminotransferase homolog TLH6 0.0031
3878 GAD1 protein GAD1 0.0031
3883 Ornithine aminotransferase variant Not Available 0.0031
306 Pyridoxal phosphate phosphatase PDXP 0.0031
664 Glutamate decarboxylase 2 GAD2 0.0031
3890 Glutamate decarboxylase 2 GAD2 0.0031
3909 Hepatic peroxysomal alanine:glyoxylate aminotransferase Not Available 0.0031
855 Sphingosine-1-phosphate lyase 1 SGPL1 0.0031
3880 Serine hydroxymethyltransferase 1 Not Available 0.0031
3910 O-phosphoseryl-tRNA(Sec) selenium transferase SEPSECS 0.0031
3894 KIAA0251 protein PDXDC1 0.0031
3875 Glycogen phosphorylase, brain form PYGB 0.0031
3882 Brain glycogen phosphorylase variant Not Available 0.0031
3903 Aminolevulinate, delta-, synthase 2 ALAS2 0.0031
3886 Migration-inducing protein 4 ALAS1 0.0031
3905 Molybdenum cofactor sulfurase MOCOS 0.0031
3913 Glutamic acid decarboxylase GAD65 0.0027
3 Histidine decarboxylase HDC 0.0027
727 Serine palmitoyltransferase 2 SPTLC2 0.0026
491 Serine palmitoyltransferase 1 SPTLC1 0.0026
184 L-serine dehydratase SDS 0.0026
431 Serine racemase SRR 0.0026
3874 Proline synthetase co-transcribed bacterial homolog protein PROSC 0.0026
89 Cysteine sulfinic acid decarboxylase CSAD 0.0026
3899 Alanine--glyoxylate aminotransferase 2-like 2 AGXT2L2 0.0026
534 Threonine synthase-like 1 THNSL1 0.0026
420 Glutamate decarboxylase 1 GAD1 0.0026
3900 Glutamate decarboxylase 1 GAD1 0.0026
665 Phosphoserine aminotransferase PSAT1 0.0026
4652 Phosphoserine aminotransferase serC 0.0026
3895 Kynurenine--oxoglutarate transaminase 3 CCBL2 0.0026
801 Kynurenine/alpha-aminoadipate aminotransferase mitochondrial AADAT 0.0026
575 2-amino-3-ketobutyrate coenzyme A ligase, mitochondrial GCAT 0.0026
455 5-aminolevulinate synthase, nonspecific, mitochondrial ALAS1 0.0026
681 Glycine dehydrogenase [decarboxylating], mitochondrial GLDC 0.0026
499 Arginine decarboxylase ADC 0.0026
435 Kynureninase KYNU 0.0024
4654 Kynureninase kynU 0.0024
763 Tyrosine aminotransferase TAT 0.0024
5493 Tyrosine aminotransferase Not Available 0.0024
169 Cysteine desulfurase, mitochondrial NFS1 0.0024
3877 Growth-inhibiting protein 18 GIG18 0.0024
358 Cystathionine beta-synthase CBS 0.0023
3884 SHMT2 protein SHMT2 0.0023
3901 SHMT2 protein SHMT2 0.0023
3885 Hypothetical protein DKFZp686P09201 DKFZp686P09201 0.0023
3879 Serine hydroxymethyltransferase 2 Not Available 0.0023
321 Serine hydroxymethyltransferase, mitochondrial SHMT2 0.0023
203 Pyridoxine-5'-phosphate oxidase PNPO 0.0023
472 Ornithine aminotransferase, mitochondrial OAT 0.0023
735 Alanine aminotransferase 1 GPT 0.0023
3904 Alanine aminotransferase 2 GPT2 0.0023
426 Aspartate aminotransferase, mitochondrial GOT2 0.0023
914 Formimidoyltransferase-cyclodeaminase FTCD 0.0022
301 Kynurenine--oxoglutarate transaminase 1 CCBL1 0.0022
114 Alanine--glyoxylate aminotransferase 2, mitochondrial AGXT2 0.0022
868 Cystathionine gamma-lyase CTH 0.0022
586 Aspartate aminotransferase, cytoplasmic GOT1 0.0021
349 Serine--pyruvate aminotransferase AGXT 0.002
795 Branched-chain-amino-acid aminotransferase, mitochondrial BCAT2 0.002
367 Serine hydroxymethyltransferase, cytosolic SHMT1 0.002
574 Branched-chain-amino-acid aminotransferase, cytosolic BCAT1 0.002
449 Ornithine decarboxylase ODC1 0.002
280 4-aminobutyrate aminotransferase, mitochondrial ABAT 0.0019
10 Glycogen phosphorylase, liver form PYGL 0.0018
1152 Glycogen phosphorylase, muscle form PYGM 0.0014
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