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Because levodopa bypasses the enzyme tyrosine hydroxylase, the rate-limiting step in dopamine synthesis, it is much more readily converted to dopamine than tyrosine, which is normally the natural precursor for dopamine production. In humans, conversion of levodopa to dopamine does not only occur within the central nervous system.
l-DOPA can be manufactured and in its pure form is sold as a drug with the INN Tooltip International Nonproprietary Name levodopa. Trade names include Sinemet, Pharmacopa, Atamet, and Stalevo. As a drug, it is used in the clinical treatment of Parkinson's disease and dopamine-responsive dystonia. l-DOPA has a counterpart with opposite chirality ...
Peripherally selective DDCIs incapable of crossing the protective blood–brain barrier (BBB) are used in augmentation of L-DOPA (levodopa) in the treatment of Parkinson's disease (PD) to block the conversion of L-DOPA into dopamine outside the brain, for the purpose of reducing adverse side effects. [3]
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 ...
In Parkinson disease, the loss of neurons from the nigrostriatum leads to the inability to convert levodopa to dopamine. The goal of AAV2-hAADC is to restore normal levels of AADC in the striatum so there could be more conversion of levodopa, and therefore reducing levodopa- induced dyskinesia. [ 6 ]
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 administered levodopa to cross the blood–brain barrier for central nervous system effect, instead of being peripherally metabolised into substances unable to cross said barrier.
[citation needed] AADC is inhibited by carbidopa outside of the blood brain barrier to inhibit the premature conversion of L-DOPA to dopamine in the treatment of Parkinson's. In humans, AADC is also the rate-limiting enzyme in the formation of trace amines.
Dopamine precursors including L-phenylalanine and L-tyrosine are used as dietary supplements. L-DOPA (Levodopa), another precursor, is used in the treatment of Parkinson's disease. Prodrugs of levodopa, including melevodopa, etilevodopa, foslevodopa, and XP-21279 also exist. They are inactive themselves but are converted into dopamine and hence ...