Levodopa

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Levodopa L-DOPA crosses the protective blood–brain barrier, whereas dopamine itself cannot. Thus, L-DOPA is used to increase dopamine concentrations in the treatment of Parkinson's disease and dopamine-responsive dystonia. This treatment was originally developed by George Cotzias and his coworkers. Once L-DOPA has entered the central nervous system, it is converted into dopamine by the enzyme aromatic L-amino acid decarboxylase, also known as DOPA decarboxylase (DDC). Pyridoxal phosphate (vitamin B6) is a required cofactor in this reaction, and may occasionally be administered along with L-DOPA, usually in the form of pyridoxine. Besides the central nervous system, L-DOPA is also converted into dopamine from within the peripheral nervous system. The resulting hyperdopaminergia causes many of the adverse side effects seen with sole L-DOPA administration. To bypass these effects, it is standard clinical practice to co-administer (with L-DOPA) a peripheral DOPA decarboxylase inhibitor (DDCI) such as carbidopa (medicines combining L-DOPA and carbidopa are branded as Lodosyn, Sinemet, Parcopa, Atamet, Stalevo) or with a benserazide (combination medicines are branded Madopar, Prolopa), to prevent the peripheral synthesis of dopamine from L-DOPA. Co-administration of pyridoxine without a DDCI accelerates the peripheral decarboxylation of L-DOPA to such an extent that it negates the effects of L-DOPA administration, a phenomenon that historically caused great confusion. In addition, L-DOPA, co-administered with a peripheral DDCI, has been investigated as a potential treatment for restless leg syndrome. However, studies have demonstrated "no clear picture of reduced symptoms".[1] The two types of response seen with administration of L-DOPA are: Short-duration response, which is related to the half-life of the drug Longer-duration response, which depends on the accumulation of effects over at least two weeks. This response is evident only in early therapy, as the inability of the brain to store dopamine is not yet a concern.