Carbidopa/levodopa

Parkinson's disease It is primarily used to improve the symptoms of Parkinson's disease but does not change the course of the disease. Other Other uses include for dopamine-responsive dystonia (DRD) and restless legs syndrome. Using carbidopa/levodopa may lead to augmentation syndrome, with increasing persistence of restless legs syndrome, and increasing severity. ==Side effects==

Common side effects include dizziness, drowsiness, blurred vision, nausea, vomiting, dry mouth, low appetite, heartburn, diarrhea, constipation, frequent sneezing, nasal congestion, flu-like symptoms, cough, muscle pain, numbness, paresthesia, sleep disturbances, skin rash, itching, or headache. Less common, but more serious, side effects can include very frequent blinking or twitching of the eyes and other forms of levodopa-induced dyskinesia (LID), fainting, mood changes (e.g., depression), confusion, hallucinations, delusions, thoughts of suicide, compulsive behavior (e.g., compulsive gambling), hypersexuality, worsening of involuntary movements or spasms, or other movement problems. == Mechanism of action ==

Levodopa is converted to dopamine via the action of a naturally occurring enzyme called DOPA decarboxylase. This occurs both in the peripheral circulation and in the central nervous system after levodopa has crossed the blood–brain barrier. Activation of central dopamine receptors improves the symptoms of Parkinson's disease; however, activation of peripheral dopamine receptors causes nausea and vomiting..\ For this reason levodopa is usually administered in combination with a DOPA decarboxylase inhibitor (DDCI), in this case carbidopa, which is very polar (and charged at physiologic pH) and cannot cross the blood–brain barrier, however prevents peripheral conversion of levodopa to dopamine and thereby reduces the unwanted peripheral side effects of levodopa. Use of carbidopa also increases the quantity of levodopa in the bloodstream that is available to enter the brain. ==History==

In 1960, the Austrian biochemist Oleh Hornykiewicz, while at the University of Vienna, examined results of autopsies of patients who had died with Parkinson's disease. He suggested that the disease was associated with, or caused by, a reduction in the levels of dopamine in the basal ganglia of the brain. Since dopamine itself did not enter the brain, he tried treating twenty patients with a racemic mixture of dihydroxyphenylalanine (DOPA), which could enter the brain and be converted there to dopamine by the action of DOPA decarboxylase. His results were positive, as were those of another trial in Montreal run by André Barbeau. Unfortunately, other investigators were unable to replicate these early results, and the use of DOPA remained in question until 1967, when George Cotzias at the Brookhaven National Laboratories in Upton, New York, used megadoses of DOPA, up to 16 grams per day. Not long after these results became known, Curt Porter at Merck showed that L-DOPA was the active stereoisomer, thus reducing the effective dose to half. ==Society and culture==

Economics It is available as a generic medication. Extended-release formulations are sold as Sinemet-CR, Rytary and Crexont. An extended-release enteral solution is sold as Duopa. Shortages In 1991, Merck licensed the rights to the manufacture and sale of Sinemet to a newly created joint venture, DuPont Merck Pharmaceutical Company. That same year, approvals for a sustained release formulation (Sinemet CR) which could be taken less frequently were also obtained. DuPont purchased Merck's share in the joint venture in 1998 and began operating the company as DuPont Pharmaceuticals (DuPont Pharma), but Merck continued to manufacture the drug for DuPont. Starting in late 2009 and continuing into 2011 Merck stopped manufacturing the drug while awaiting regulatory approvals due to a change in the supplier of the active ingredient. This resulted in shortages of the brand name products Sinemet and Sinemet CR, although alternative generic versions were still available. == References ==