Carbidopa

Carbidopa

Systematic (IUPAC) name
(2S)-3-(3,4-dihydroxyphenyl)-2-hydrazino-2-methylpropanoic acid
Clinical data
Trade names	Lodosyn
AHFS/Drugs.com	monograph
Licence data	US FDA:link
Pregnancy cat.	?
Legal status	POM (UK)
Pharmacokinetic data
Protein binding	76%
Metabolism	decarboxylated to dopamine in extracerebral tissues
Half-life	2 hours
Identifiers
CAS number	28860-95-9 Y
ATC code	?
PubChem	CID 34359
DrugBank	APRD00160
ChemSpider	31640 Y
UNII	KR87B45RGH Y
KEGG	D00558 Y
ChEBI	CHEBI:39585 Y
ChEMBL	CHEMBL1201236 N
Chemical data
Formula	C10H14N2O4
Mol. mass	226.229 g/mol
SMILES	eMolecules & PubChem
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 Y Key:TZFNLOMSOLWIDK-JTQLQIEISA-N Y
N(what is this?)  (verify)

Carbidopa (Lodosyn) is a drug given to people with Parkinson's disease in order to inhibit peripheral metabolism of levodopa. This property is significant in that it allows a greater proportion of peripheral levodopa to cross the blood brain barrier for central nervous system effect.

Pharmacology

Carbidopa inhibits aromatic-L-amino-acid decarboxylase (DOPA Decarboxylase or DDC), an enzyme important in the biosynthesis of L-tryptophan to serotonin and in the biosynthesis of L-DOPA to Dopamine (DA). DDC exists both outside of (body periphery) and within the confines of the blood-brain barrier.

Carbidopa is used in the treatment, among other diseases, of Parkinson's disease (PD), a condition where patients lack sufficient brain dopamine. The pharmacologic objective is to get an exogenous dopamine-precursor known as levodopa/L-DOPA into the dopamine-deficient brains of PD patients. Levodopa/L-DOPA can cross the blood brain barrier, but dopamine cannot. The use of carbidopa seems counter-intuitive in Parkinson's disease (PD) in that it prevents DDC conversion of levodopa/L-DOPA to dopamine. However, exogenously provided levadopa/L-DOPA gets metabolized peripherally to its active metabolite dopamine before reaching the blood-brain barrier. Therefore, the PD brain, which is deficient in dopamine, will not receive as much of its prodrug precursor levodopa/L-DOPA due to peripheral DDC breakdown. However, carbidopa, can decrease peripheral DDC conversion of levodopa/L-DOPA before it crosses the blood-brain barrier. Carbidopa acts as a peripheral DDC inhibitor, as carbidopa, itself, cannot cross the blood-brain barrier. In other words, carbidopa has no effect on brain DDC conversion of levodopa/L-DOPA to dopamine. Ultimately, a greater proportion of the exogenously provided levodopa/L-DOPA reaches the brain. Commercially, carbidopa/levodopa combinations are available in the treatment of central dopamine deficiencies.

Along with carbidopa, other DDC inhibitors are benserazide (Ro-4-4602), difluromethyldopa, and α-methyldopa.

Uses

Used in tandem with L-DOPA (trade name levodopa, a dopamine precursor converted in the body to dopamine), it increases the plasma half-life of levodopa from 50 minutes to 1½ hours. CarbiDOPA cannot cross the blood brain barrier, so it inhibits only peripheral DDC. It thus prevents the conversion of L-DOPA to dopamine peripherally. This reduces the side effects caused by dopamine on the periphery, as well as increasing the concentration of L-DOPA and dopamine in the brain.

The combination of carbidopa/levodopa carries the brand names of Sinemet, Parcopa and Atamet; while Stalevo is a combination with entacapone, which enhances the bioavailability of carbidopa and levodopa.

Carbidopa is also used in combination with 5-HTP, a naturally occurring amino acid which is a precursor to the neurotransmitter serotonin and an intermediate in tryptophan metabolism. Carbidopa prevents 5-HTP's metabolism in the liver and the resulting elevated levels of serotonin in the blood. Research shows that co-administration of 5-HTP and carbidopa greatly increases plasma 5-HTP levels. 5-HTP has no reported cases of heart valve disease associated with it as found in the peer reviewed literature; however, several cases of scleroderma-like illness have been reported in patients using carbidopa and 5-HTP. In Europe, 5-HTP is prescribed with carbidopa to prevent the conversion of 5-HTP into serotonin until it reaches the brain.

External links

• Lodosyn prescribing information
• Sinemet datasheet for New Zealand