DOPA Decarboxylase Inhibitor
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An aromatic L-amino acid decarboxylase inhibitor (synonyms: DOPA decarboxylase inhibitor, Extracerebral decarboxylase inhibitor, DDCI and AAADI) is a
medication A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the medical field and ...
of type
enzyme inhibitor An enzyme inhibitor is a molecule that binds to an enzyme and blocks its activity. Enzymes are proteins that speed up chemical reactions necessary for life, in which substrate molecules are converted into products. An enzyme facilitates a sp ...
which inhibits the synthesis of dopamine by the
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
aromatic L-amino acid decarboxylase Aromatic L-amino acid decarboxylase (AADC or AAAD), also known as DOPA decarboxylase (DDC), tryptophan decarboxylase, and 5-hydroxytryptophan decarboxylase, is a lyase enzyme (), located in region 7p12.2-p12.1. Mechanism The enzyme uses pyrid ...
(AADC, AAAD, or DOPA decarboxylase). It is used to inhibit the decarboxylation of
L-DOPA -DOPA, also known as levodopa and -3,4-dihydroxyphenylalanine, is an amino acid that is made and used as part of the normal biology of some plants and animals, including humans. Humans, as well as a portion of the other animals that utilize -DOPA ...
to dopamine outside the brain, i.e. in the
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the cir ...
. This is primarily co-administered with L-DOPA to combat
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
. Administration can prevent common side-effects, such as nausea and vomiting, as a result of interaction with D2 receptors in the vomiting center (or cheomoreceptor trigger zone) located outside the blood–brain barrier. Examples of extracerebral decarboxylase inhibitors include
carbidopa 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–br ...
and
benserazide Benserazide (also called Serazide or Ro 4-4602) is a peripherally acting aromatic L-amino acid decarboxylase or DOPA decarboxylase inhibitor, which is unable to cross the blood–brain barrier. It is on the World Health Organization's List of ...
.


Indications

Peripherally selective Peripherally selective drugs have their primary mechanism of action outside of the central nervous system (CNS), usually because they are excluded from the CNS by the blood–brain barrier. By being excluded from the CNS, drugs may act on the rest ...
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 Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
(PD) to block the conversion of L-DOPA into dopamine outside the brain, for the purpose of reducing adverse side effects. Combined L-DOPA and DDCI therapy does not inherently decrease peripheral cardiovascular side effects of L-DOPA administration; however, combined therapy potentiates the central effects of L-DOPA by decreasing the dose-dependency 4-5 fold, therein allowing for effective Parkinson's disease treatment without cardiovascular risk associated with high peripheral dopamine.Yahr, M. D., in Advances in Neurology, ed. M. D. Yahr, p. vi, vol. 2. New York, Raven Press, 1973.


List of DDCIs

*
Benserazide Benserazide (also called Serazide or Ro 4-4602) is a peripherally acting aromatic L-amino acid decarboxylase or DOPA decarboxylase inhibitor, which is unable to cross the blood–brain barrier. It is on the World Health Organization's List of ...
(Madopar, Prolopa, Modopar, Madopark, Neodopasol, EC-Doparyl, etc.) *
Carbidopa 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–br ...
(Lodosyn, Sinemet, Pharmacopa, Atamet, Stalevo, etc.) *
Methyldopa Methyldopa, sold under the brand name Aldomet among others, is a medication used for high blood pressure. It is one of the preferred treatments for high blood pressure in pregnancy. For other types of high blood pressure including very high blo ...
(Aldomet, Aldoril, Dopamet, Dopegyt, etc.) *
alpha-Difluoromethyl-DOPA α-Difluoromethyl-DOPA (DFMD, DFM-DOPA) is a DOPA decarboxylase inhibitor. See also * Carbidopa * Methyldopa Methyldopa, sold under the brand name Aldomet among others, is a medication used for high blood pressure. It is one of the preferr ...
(DFMD) *3',4',5,7-Tetrahydroxy-8-methoxyisoflavone 8262-89-8*
Epigallocatechin gallate Epigallocatechin gallate (EGCG), also known as epigallocatechin-3-gallate, is the ester of epigallocatechin and gallic acid, and is a type of catechin. EGCG – the most abundant catechin in tea – is a polyphenol under basic research for its ...
(EGCG) *
Epigallocatechin Gallocatechol or gallocatechin (GC) is a flavan-3-ol, a type of chemical compound including catechin, with the gallate residue being in an isomeric trans position. This compound possesses two epimers. The most common, (+)-gallocatechin (GC), CAS ...
(EGC)


References

* {{Nervous-system-drug-stub