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L-dihydroxyphenylalanine : ウィキペディア英語版
L-DOPA

L-DOPA ( or ) (alt., L-3,4-dihydroxyphenylalanine) is a chemical that is made and used as part of the normal biology of humans, some animals and plants. Some animals and humans make it via biosynthesis from the amino acid L-tyrosine. L-DOPA is the precursor to the neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline) collectively known as catecholamines. Furthermore, L-DOPA itself mediates neurotrophic factor release by the brain and CNS.〔Citation: Lopez VM, Decatur CL, Stamer WD, Lynch RM, McKay BS (2008) L-DOPA is an endogenous ligand for OA1. PLoS Biol 6(9): e236. doi:10.1371/journal.pbio.0060236〕〔Hiroshima Y1, Miyamoto H, Nakamura F, et al. Br J Pharmacol. 2014 Jan;171(2):403-14. doi: 10.1111/bph.12459. http://www.ncbi.nlm.nih.gov/pubmed/24117106.〕 L-DOPA can be manufactured and in its pure form is sold as a psychoactive drug with the INN levodopa; trade names include Sinemet, Parcopa, Atamet, Stalevo, Madopar, and Prolopa. 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, D-DOPA. As is true for many molecules, the human body produces only one of these isomers (the L-DOPA form).
==Medical use==
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 made practical and proven clinically by George Cotzias and his coworkers, for which they won the 1969 Lasker Prize.〔(Lasker Award 1969 Description ), accessed April 1, 2013〕〔Tanya Simuni and Howard Hurtig. "Levadopa: A Pharmacologic Miracle Four Decades Later", in (Parkinson's Disease: Diagnosis and Clinical Management ) (Google eBook). Eds. Stewart A Factor and William J Weiner. Demos Medical Publishing, 2008〕 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. 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. Excessive peripheral dopamine signaling causes many of the adverse side effects seen with sole L-DOPA administration. To bypass these effects, it is standard clinical practice to coadminister (with L-DOPA) a peripheral DOPA decarboxylase inhibitor (DDCI) such as carbidopa (medicines containing carbidopa, either alone or in combination with L-DOPA, are branded as Lodosyn (Aton Pharma) Sinemet (Merck Sharp & Dohme Limited), Parcopa (Jazz Pharmaceuticals), Atamet (UCB), and Stalevo (Orion Corporation) or with a benserazide (combination medicines are branded Madopar or Prolopa), to prevent the peripheral synthesis of dopamine from L-DOPA. Coadministration 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".
The two types of response seen with administration of L-DOPA are:
* The short-duration response is related to the half-life of the drug.
* The longer-duration response depends on the accumulation of effects over at least two weeks, during which ΔFosB accumulates in nigrostriatal neurons. In the treatment of Parkinson's disease, this response is evident only in early therapy, as the inability of the brain to store dopamine is not yet a concern.

抄文引用元・出典: フリー百科事典『 ウィキペディア(Wikipedia)
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