CARBIDOPA ANHYDROUS

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C10H14N2O4
Molecular Weight	226.2292
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@@](CC1=CC(O)=C(O)C=C1)(NN)C(O)=O

InChI

InChIKey=TZFNLOMSOLWIDK-JTQLQIEISA-N

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

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/017830s014s016s017s018s019s030lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/10934669

Carbidopa is a competitive inhibitor of aromatic L-amino acid decarboxylase that does not cross the blood-brain barrier, is routinely administered with levodopa (LD) for the treatment of the symptoms of idiopathic Parkinson’s disease (paralysis agitans), postencephalitic parkinsonism, and symptomatic parkinsonism, which may follow injury to the nervous system by carbon monoxide intoxication and/or manganese intoxication. Current evidence indicates that symptoms of Parkinson’s disease are related to depletion of dopamine in the corpus striatum. Administration of dopamine is ineffective in the treatment of Parkinson’s disease apparently because it does not cross the blood-brain barrier. However, levodopa, the metabolic precursor of dopamine, does cross the blood- brain barrier, and presumably is converted to dopamine in the brain. When levodopa is administered orally it is 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. For this reason, large doses of levodopa are required for adequate therapeutic effect and these may often be accompanied by nausea and other adverse reactions, some of which are attributable to dopamine formed in extracerebral tissues. Carbidopa inhibits decarboxylation of peripheral levodopa. Carbidopa has not been demonstrated to have any overt pharmacodynamic actions in the recommended doses.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DOPA decarboxylase 15 Target ID: CHEMBL1843 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11106255	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Idiopathic Parkinson's disease 19 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/017830s014s016s017s018s019s030lbl.pdf	Palliative		Approved 8583	LODOSYN Approved Use LODOSYN is indicated for use with carbidopa-levodopa or with levodopa in the treatment of the symptoms of idiopathic Parkinson’s disease (paralysis agitans), postencephalitic parkinsonism, and symptomatic parkinsonism, which may follow injury to the nervous system by carbon monoxide intoxication and/or manganese intoxication. LODOSYN is for use with carbidopa-levodopa in patients for whom the dosage of carbidopa-levodopa provides less than adequate daily dosage (usually 70 mg daily) of carbidopa. LODOSYN is for use with levodopa in the occasional patient whose dosage requirement of carbidopa and levodopa necessitates separate titration of each medication. LODOSYN is used with carbidopa-levodopa or with levodopa to permit the administration of lower doses of levodopa with reduced nausea and vomiting, more rapid dosage titration, and with a somewhat smoother response. However, patients with markedly irregular (“on-off”) responses to levodopa have not been shown to benefit from the addition of carbidopa. Since carbidopa prevents the reversal of levodopa effects caused by pyridoxine, supplemental pyridoxine (vitamin B6), can be given to patients when they are receiving carbidopa and levodopa concomitantly or as carbidopa-levodopa. Launch Date 1977

C_max

Value	Dose	Co-administered	Analyte	Population
108.57 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30295551	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered: LEVODOPA	LEVODOPA	CARBIDOPA plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
559.92 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30295551	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered: LEVODOPA	LEVODOPA	CARBIDOPA plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.09 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30295551	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered: LEVODOPA	LEVODOPA	CARBIDOPA plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
64% DRUG LABEL https://www.drugs.com/monograph/levodopa-carbidopa.html			CARBIDOPA plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BSEP 550 CYP2C19 2057 MRP4 290 MRP3 246 CYP1A2 2153 MRP2 499 P-gp 1741 BCRP 910 CYP19A1 429 CYP2A6 879 CYP2E1 1060 UMAT 30		CYP1B1 71 CYP1A2 832 CYP1A1 151

Drug as perpetrator

Target	Modality	Activity
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=225144194	inconclusive [IC50 11.9877 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=225144194	inconclusive [IC50 30.1116 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/410#sid=11113507	inconclusive [IC50 7.943 uM]
CYP2A6 911	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/625246#sid=103770731	no [IC50 >10 uM]
CYP2E1 1146	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/625250#sid=103770731	no [IC50 >10 uM]
BSEP 554	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]
MRP2 625	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]
MRP3 326	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]
MRP4 345	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]
BCRP 985	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1325#sid=8139862	no
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/743139#sid=144204461	no
CYP2C19 2141	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/899#sid=11113507	no
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/891#sid=11113507	no
MRP1 232	activator 342 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/799#sid=8139862	no
P-gp 1932	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1326#sid=8139862	no
UMAT 30	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/602162#sid=93576631	no
AHR 9	activator 342 Sources: https://pubmed.ncbi.nlm.nih.gov/28963435/	yes
CYP1A1 272	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/28963435/	yes
CYP1A2 2333	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/28963435/	yes
CYP1B1 93	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/28963435/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/588834#sid=50104417

PubMed

Title	Date	PubMed
Effect of dopamine agonists and antagonists on the lorazepam withdrawal syndrome in rats.	2000 Mar	10744342
Levodopa induces dyskinesias in normal squirrel monkeys.	2001 Aug	11506410
L-dopa induces dyskinesia in normal monkeys: behavioural and pharmacokinetic observations.	2001 Aug	11498717
L-DOPA and glia-conditioned medium have additive effects on tyrosine hydroxylase expression in human catecholamine-rich neuroblastoma NB69 cells.	2001 Aug	11483656
Duodenal levodopa infusion in Parkinson's disease--long-term experience.	2001 Dec	11903087
Case report: successful use of rectally administered levodopa-carbidopa.	2001 Jan	11212422
A novel neurodevelopmental syndrome responsive to 5-hydroxytryptophan and carbidopa.	2001 Jun	11386854
Visual acuities after levodopa administration in amblyopia.	2001 Mar-Apr	11310708
Structural insight into Parkinson's disease treatment from drug-inhibited DOPA decarboxylase.	2001 Nov	11685243
Dopamine mediates striatal malonate toxicity via dopamine transporter-dependent generation of reactive oxygen species and D2 but not D1 receptor activation.	2001 Oct	11595758
Post-stroke violent adventitial movement responsive to levo-dopa/carbi-dopa therapy.	2001 Oct	11595087
Dopaminergic therapy with carbidopa L-dopa for left neglect after stroke: a case series.	2001 Sep	11552204
Stereoselective effect of (R)- and (S)-1-methyl-1,2,3,4-tetrahydroisoquinolines on a mouse model of Parkinson's disease.	2001 Sep 1	11604249
Atypical presentation of dopa-responsive dystonia: generalized hypotonia and proximal weakness.	2001 Sep 25	11571350
Clinical management of neuroleptic malignant syndrome.	2001 Winter	11525080
Restless legs syndrome in the older adult: diagnosis and management.	2002	12390051
[The use of amantadine sulfate in combined therapy of Parkinson's disease].	2002	12161861
[Serotonin syndrome: report of a fatal case and review of the literature].	2002 Apr	12003730
Role of adenosine in drug-induced catatonia in mice.	2002 Aug	12597016
Acute dopaminergic challenge tests to assess postural/kinetic tremor of different origin: a case report.	2002 Aug	12122189
Semicarbazide-sensitive amine oxidase (SSAO) gene expression in alloxan-induced diabetes in mice.	2002 Dec	12606817
Levodopa-carbidopa with occlusion in older children with amblyopia.	2002 Dec	12506278
Screening for tetrahydrobiopterin deficiency among hyperphenylalaninemia patients in Southern China.	2002 Feb	11940335
Brain catecholamine metabolism in catechol-O-methyltransferase (COMT)-deficient mice.	2002 Jan	11849292
A double-blind crossover, placebo-controlled study of the adenosine A2A antagonist theophylline in Parkinson's disease.	2002 Jan-Feb	11852293
[Hallucinations caused by paroxetine in combined usage of levodopa-carbidopa].	2002 Jun 1	12073510
In vivo metabolism and partitioning of 6-[18F]fluoro-L-meta-tyrosine in whole blood: a unified compartment model.	2002 Jun 7	12108778
Parkinson's disease. Therapeutic strategies to improve patient function and quality of life.	2002 Mar	11899548
Influence of layer position on in vitro and in vivo release of levodopa methyl ester and carbidopa from three-layer matrix tablets.	2002 Mar	11880007
Levodopa plus carbidopa before physiotherapy increased motor recovery after stroke.	2002 Mar-Apr	11874277
Gender and pramipexole effects on levodopa pharmacokinetics and pharmacodynamics.	2002 May 14	12011296
Clozapine withdrawal symptoms in a Parkinson's disease patient.	2002 Nov	12465085
Levodopa but not ropinirole induces an internalization of D1 dopamine receptors in parkinsonian rats.	2002 Nov	12465054
Repeated administration of piribedil induces less dyskinesia than L-dopa in MPTP-treated common marmosets: a behavioural and biochemical investigation.	2002 Sep	12360537
Olanzapine: a proarrhythmic drug?	2002 Sep	12355682
Viral encephalitis complicated by neuroleptic malignant syndrome in a 7-year-old girl.	2003 Apr	12698035
Quercetin potentiates L-Dopa reversal of drug-induced catalepsy in rats: possible COMT/MAO inhibition.	2003 Jun	12711835
Commonly used L-amino acid decarboxylase inhibitors block monoamine oxidase activity in the rat.	2003 Mar	12658372
Randomized trial of pallidotomy versus medical therapy for Parkinson's disease.	2003 May	12730989
Effect of pulsatile administration of levodopa on dyskinesia induction in drug-naïve MPTP-treated common marmosets: effect of dose, frequency of administration, and brain exposure.	2003 May	12722161
Optimizing levodopa pharmacokinetics: intestinal infusion versus oral sustained-release tablets.	2003 May-Jun	12782919
Parkinsonian speech disfluencies: effects of L-dopa-related fluctuations.	2003 Spring	12706913

Patents

Sample Use Guides

In Vivo Use Guide

Whether given with carbidopa-levodopa or with levodopa, the optimal daily dose of LODOSYN (CARBIDOPA tablets) must be determined by careful titration. Most patients respond to a 1:10 proportion of carbidopa and levodopa, provided the daily dosage of carbidopa is 70 mg or more a day. The maximum daily dosage of carbidopa should not exceed 200 mg, since clinical experience with larger dosages is limited. If the patient is taking carbidopa-levodopa, the amount of carbidopa in carbidopa-levodopa should be considered when calculating the total amount of LODOSYN to be administered each day.

Route of Administration: Oral

In Vitro Use Guide

It was evaluated the effect of carbidopa on 6-18F-fluoro-3,4-dihydroxy-l-phenylalanine (18F-FDOPA) uptake in the murine β-cell line RIN-m5F. Incubation of RIN-m5F cells with 80 μM carbidopa did not significantly affect the cellular accumulation of 18F-FDOPA.

Name

Type

Language

CARBIDOPA ANHYDROUS

Common Name

English

BENZENEPROPANOIC ACID, .ALPHA.-HYDRAZINO-3,4-DIHYDROXY-.ALPHA.-METHYL-, (S)-

Preferred Name

English

carbidopa [INN]

Common Name

English

Carbidopa [WHO-DD]

Common Name

English

CARBIDOPA, L- ANHYDROUS

Common Name

English

CARBIDOPA ANHYDROUS [MI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C38149