Carbidopa

Carbidopa
Fvasconcellos · Public domain · source
IUPAC name	(2S)-3-(3,4-dihydroxyphenyl)-2-hydrazinyl-2-methylpropanoic acid
Tradename	Lodosyn, others
Drugs.com	Monograph
MedlinePlus	a601068
Pregnancy AU	B3
Legal AU	S4
Legal CA	Rx-only
Legal UK	POM
Legal US	Rx-only
Legal status	Rx-only
Routes of administration	By mouth
Bioavailability	25–30%
Protein bound	76%
Metabolism	Not extensively metabolized
Elimination half-life	2 hours
Excretion	Kidney (53% unchanged)
CAS number	28860-95-9
PubChem	34359
ChemSpider	31645
UNII	MNX7R8C5VO
ChEBI	3380
ChEMBL	1200730
Chemical formula	C10H14N2O4
Molecular weight	226.23 g·mol−1

Carbidopa is a peripheral aromatic L-amino acid decarboxylase inhibitor used in the management of Parkinson's disease. It is almost exclusively administered in combination with levodopa, a precursor to the neurotransmitter dopamine, to enhance the delivery of levodopa to the central nervous system. This combination therapy, available under brand names like Sinemet and Stalevo, forms a cornerstone of treatment for the motor symptoms of Parkinson's disease, such as bradykinesia, rigidity, and tremor.

Medical uses

Carbidopa is co-administered with levodopa to treat the motor symptoms of Parkinson's disease and dopamine-responsive dystonia. It is also used in the management of restless legs syndrome when standard therapies are insufficient. By inhibiting the peripheral conversion of levodopa, it allows a greater proportion of the dose to reach the blood-brain barrier, thereby reducing the required oral dose of levodopa and mitigating peripheral side effects like nausea and vomiting. Fixed-dose combination products, such as those marketed by Merck & Co. under the name Sinemet, are the most common method of administration.

Pharmacology

Carbidopa acts as an irreversible inhibitor of the enzyme aromatic L-amino acid decarboxylase (AADC). This enzyme is responsible for converting levodopa to dopamine in peripheral tissues, such as those in the gastrointestinal tract and capillary endothelium. By blocking this conversion outside the central nervous system, carbidopa increases the bioavailability of levodopa for transport across the blood-brain barrier via the large neutral amino acid transporter. Once in the brain, levodopa is decarboxylated to dopamine, compensating for the depleted dopaminergic neurons in the substantia nigra. Carbidopa itself does not cross the blood-brain barrier to a significant degree.

Adverse effects

When used with levodopa, carbidopa can contribute to side effects associated with increased central dopaminergic activity. These include dyskinesia, hallucinations, orthostatic hypotension, and sleep disturbances. Because carbidopa reduces peripheral dopamine formation, it can alleviate gastrointestinal issues like nausea caused by levodopa alone. However, rare but serious adverse effects reported include symptoms of neuroleptic malignant syndrome upon abrupt withdrawal and, with long-term use, potential cardiac effects noted in some patients at the Mayo Clinic.

History

The development of carbidopa followed the discovery of levodopa's efficacy in treating Parkinson's disease by George Cotzias in the 1960s. Researchers at Merck & Co. sought to address the high peripheral metabolism of levodopa, which caused significant side effects and limited its utility. Carbidopa was synthesized as a structural analog of levodopa designed to inhibit the aromatic L-amino acid decarboxylase enzyme. Its introduction in the 1970s, notably in the fixed-dose combination Sinemet, revolutionized Parkinson's therapy by making levodopa treatment more tolerable and effective, a milestone recognized by organizations like the American Academy of Neurology.

Society and culture

Carbidopa is available under various brand names worldwide, including Lodosyn as a single entity and in combinations like Sinemet and Stalevo. It is on the World Health Organization's List of Essential Medicines. The drug's development and marketing have involved major pharmaceutical companies such as Merck & Co. and Orion Corporation. The combination therapy's impact on managing Parkinson's disease has been a significant subject in medical literature and patient advocacy, featured in publications by the Michael J. Fox Foundation and discussed at forums like the International Congress of Parkinson's Disease and Movement Disorders.

Category:Dopaminergic antiparkinsonian agents Category:Merck & Co. brands Category:World Health Organization essential medicines