General
Preferred name
CARBIDOPA
Synonyms
(S)-(-)-Carbidopa ()
S(-)-CARBIDOPA ()
Carbidopa Hydrate ()
CARBIDOPA ANHYDROUS ()
(S)-Carbidopa ()
Carbidopa (monohydrate) ()
(S)-(-)-Carbidopa (monohydrate) ()
Lodosyn ()
Carbidopa monohydrate ()
NSC-758190 ()
Carbidopum monohydrate ()
MK-486 ()
NSC-751137 ()
Carbidopa (hydrate) ()
Carbidopa-d3 (hydrate) ()
P&D ID
PD001371
CAS
38821-49-7
28860-95-9
27925-91-3
14585-65-0
1426847-87-1
1276197-58-0
Tags
natural product
drug
available
Approved by
EMA
FDA
First approval
1975
Drug Status
approved
Drug indication
Inhibitor (decarboxylase)
Parkinson disease
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
MOA
Carbidopa is an inhibitor of the DDC which in order, inhibits the peripheral metabolism of levodopa.[A173935] DDC is very important in the biosynthesis of L-tryptophan to serotonin and the modification of L-DOPA to dopamine.[A13607] DDC can be found in the body periphery and in the blood-brain barrier.[A13607] The action of carbidopa is focused on peripheral DDC as this drug cannot cross the blood-brain barrier.[T28] 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.
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.[FDA label] The combination therapy is administered for the reduction of [levodopa]-driven nausea and vomiting.[FDA label] The product of carbidopa should be used in patients where the combination therapy of carbidopa/[levodopa] provide less than the adequate daily dosage.[FDA label] As well carbidopa can be used in patients where the dosages of carbidopa and [levodopa] require individual titration.[FDA label]
ROE
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.[A274]
ABSORPTION
When [levodopa]/carbidopa is administered orally, 40-70% of the administered dose is absorbed.[L5116] Once absorbed, carbidopa shows bioavailability of 58%.[A173941] A maximum concentration of 0.085 mcg/ml was achieved after 143 min with an AUC of 19.28 mcg.min/ml.[A173944]
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.[FDA 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.[FDA label]
HALF-LIFE
The reported half-life of carbidopa is of approximately 107 minutes.[A173944]
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).[A274]
MOA
Carbidopa is an inhibitor of the DDC which in order, inhibits the peripheral metabolism of levodopa.[A173935] DDC is very important in the biosynthesis of L-tryptophan to serotonin and the modification of L-DOPA to dopamine.[A13607] ; ; DDC can be found in the body periphery and in the blood-brain barrier.[A13607] The action of carbidopa is focused on peripheral DDC as this drug cannot cross the blood-brain barrier.[T28] 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.
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.[FDA label]; ; The combination therapy is administered for the reduction of [levodopa]-driven nausea and vomiting.[FDA label]; ; The product of carbidopa should be used in patients where the combination therapy of carbidopa/[levodopa] provide less than the adequate daily dosage.[FDA label]; ; As well carbidopa can be used in patients where the dosages of carbidopa and [levodopa] require individual titration.[FDA label]
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.[FDA 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.[FDA label]
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].[A13607] 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.[T28] 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.[T394]
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].[A13607]; ; 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.[T28] 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.[T394]
DESCRIPTION
Carbidopa was originally approved by the FDA in combination with in 1975. It is an inhibitor of L-Aromatic amino-acid decarboxylase (a.k.a. L-Dopa decarboxylase) that decreases the peripheral decarboxylation of levodopa to dopamine. The competitive or noncompetitive nature of carbidopa's interaction with L-Dopa decarboxylase is complex. Two published papers that discuss the kinetics of the inhibitor/enzyme interaction are and , and from analysis of these it would appear that due to the slow dissociation of carbidopa from L-Dopa decarboxylase, once the enzyme/inhibitor complex has formed substrate is unable to displace the inhibitor. Carbidopa is described as a competitive inhibitor in these articles .
(GtoPdb)
DESCRIPTION
Aromatic L-amino acid decarboxylase inhibitor
(Tocriscreen Total)
DESCRIPTION
Spermine and spermidine acetyltransferase potentiator
(Tocris Bioactive Compound Library)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
0
Organisms
1
Compound Sets
31
AdooQ Bioactive Compound Library
ChEMBL Approved Drugs
ChEMBL Drugs
Concise Guide to Pharmacology 2017/18
Concise Guide to Pharmacology 2019/20
Concise Guide to Pharmacology 2021/22
Concise Guide to Pharmacology 2023/24
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
Enamine BioReference Compounds
Guide to Pharmacology
LSP-MoA library (Laboratory of Systems Pharmacology)
Mcule NIBR MoA Box Subset
NCATS Inxight Approved Drugs
Novartis Chemogenetic Library (NIBR MoA Box)
NPC Screening Collection
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
The Spectrum Collection
Tocris Bioactive Compound Library
Tocriscreen Total
ZINC Tool Compounds
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
64
Molecular Weight
226.1
Hydrogen Bond Acceptors
5
Hydrogen Bond Donors
5
Rotatable Bonds
4
Ring Count
1
Aromatic Ring Count
1
cLogP
-0.05
TPSA
115.81
Fraction CSP3
0.3
Chiral centers
1.0
Largest ring
6.0
QED
0.28
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Pathway
Metabolism
Immunology/Inflammation
Target
Aromatic-L-amino-acid decarboxylase
DDC
Aryl hydrocarbon receptor
Decarboxylase
Primary Target
Decarboxylases
MOA
Inhibitor
Dopa decarboxylase inhibitor
aromatic L-amino acid decarboxylase inhibitor
Member status
virtual
Indication
Parkinson's Disease
Therapeutic Class
Antiparkinson Agents
Source data
