Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/11/28 09:54:19」(JST)
wiki en
| Systematic (IUPAC) name | |
|---|---|
| (2S)-3-(3,4-dihydroxyphenyl)-2-hydrazino-2-methylpropanoic acid | |
| Clinical data | |
| Trade names | Lodosyn |
| AHFS/Drugs.com | monograph |
| Licence data | US FDA:link |
| Pregnancy cat. | ? |
| Legal status | POM (UK) ℞-only (US) |
| Pharmacokinetic data | |
| Protein binding | 76% |
| Metabolism | decarboxylated to dopamine in extracerebral tissues |
| Half-life | 2 hours |
| Identifiers | |
| CAS number | 28860-95-9 Y |
| ATC code | ? |
| PubChem | CID 34359 |
| DrugBank | DB00190 |
| ChemSpider | 31640 Y |
| UNII | KR87B45RGH Y |
| KEGG | D00558 Y |
| ChEBI | CHEBI:39585 Y |
| ChEMBL | CHEMBL1201236 N |
| Chemical data | |
| Formula | C10H14N2O4 |
| Mol. mass | 226.229 g/mol |
|
SMILES
|
|
|
InChI
|
|
| N (what is this?) (verify) |
|
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 peripheral levodopa to cross the blood brain barrier for central nervous system effect.
Contents
- 1 Pharmacology
- 2 Uses
- 3 References
- 4 External links
Pharmacology[edit]
Carbidopa inhibits aromatic-L-amino-acid decarboxylase (DOPA Decarboxylase or DDC),[1] an enzyme important in the biosynthesis of L-tryptophan to serotonin and in the biosynthesis of L-DOPA to Dopamine (DA). DDC exists both outside of (body periphery) and within the confines of the blood–brain barrier.
Carbidopa is used in the treatment of, among other diseases, Parkinson's disease (PD), a condition characterized by death of dopaminergic neurons in the substantia nigra. Increased dopamine available may increase the effectiveness of the remaining neurons and alleviate symptoms for a time. The pharmacologic objective is to get an exogenous dopamine-precursor known as levodopa/L-DOPA into the dopamine-deficient brains of PD patients. Levodopa/L-DOPA can cross the blood brain barrier, but dopamine cannot. The use of carbidopa seems counter-intuitive in Parkinson's disease (PD) in that it prevents DDC conversion of levodopa/L-DOPA to dopamine. However, exogenously provided, levadopa/L-DOPA gets metabolized peripherally to its active metabolite dopamine before reaching the blood–brain barrier. Therefore, the PD brain, which is deficient in dopamine, will not receive as much of its prodrug precursor levodopa/L-DOPA due to peripheral DDC breakdown. However, carbidopa can decrease peripheral DDC conversion of levodopa/L-DOPA before it crosses the blood–brain barrier. Carbidopa acts as a peripheral DDC inhibitor, as carbidopa, itself, cannot cross the blood–brain barrier. In other words, carbidopa has no effect on brain DDC conversion of levodopa/L-DOPA to dopamine. Ultimately, a greater proportion of the exogenously provided levodopa/L-DOPA reaches the brain. Commercially, carbidopa/levodopa combinations are available in the treatment of central dopamine deficiencies.
Along with carbidopa, other DDC inhibitors are benserazide (Ro-4-4602), difluromethyldopa, and α-methyldopa.
Uses[edit]
Carbidopa, an inhibitor of aromatic amino acid decarboxylation, is a white, crystalline compound, slightly soluble in water, with a molecular weight of 244.3. It is designated chemically as (—)-L-α-hydrazino-α-methyl-β-(3,4-dihydroxybenzene) propanoic acid monohydrate. Its empirical formula is C10H14N2O4•H2O. Used in tandem with L-DOPA (also known as levodopa, a dopamine precursor converted in the body to dopamine), it increases the plasma half-life of levodopa from 50 minutes to 1½ hours. CarbiDOPA cannot cross the blood brain barrier, so it inhibits only peripheral DDC. It thus prevents the conversion of L-DOPA to dopamine peripherally. This reduces the side effects caused by dopamine on the periphery, as well as increasing the concentration of L-DOPA and dopamine in the brain.
The combination of carbidopa/levodopa carries the brand names of Kinson,Sinemet, Parcopa and Atamet; while Stalevo is a combination with entacapone, which enhances the bioavailability of carbidopa and levodopa.
Carbidopa is most commonly used as a method to inhibit the activity of dopamine decarboxylase. This is an enzyme that breaks down L-Dopa in the periphery and converts it to dopamine. This results in the newly formed dopamine being unable to cross the blood brain barrier and the effectiveness of and L-Dopa treatments is greatly decreased. Carbidopa reduces the amount of levodopa required to produce a given response by about 75% and, when administered with levodopa, increases both plasma levels and the plasma half-life of levodopa, and decreases plasma and urinary dopamine and homovanillic acid. Elimination half-life of levodopa in the presence of carbidopa is about 1.5 hours. Following SINEMET CR, the apparent half-life of levodopa may be prolonged because of continuous absorption. This is extremely useful in the treatment of parkinsons disease symptoms because the amount of levodopa administered to the patient can be greatly reduced.This reduction in dosage is extremely useful due to the side effects that may occur from an overdose of L-Dopa within the body.
Carbidopa is also used in combination with 5-HTP, a naturally occurring amino acid which is a precursor to the neurotransmitter serotonin and an intermediate in tryptophan metabolism. Carbidopa prevents 5-HTP's metabolism in the liver and the resulting elevated levels of serotonin in the blood. Research shows that co-administration of 5-HTP and carbidopa greatly increases plasma 5-HTP levels. 5-HTP has no reported cases of heart valve disease associated with it as found in the peer reviewed literature;[2][3] however, several cases of scleroderma-like illness have been reported in patients using carbidopa and 5-HTP.[4] In Europe, 5-HTP is prescribed with carbidopa to prevent the conversion of 5-HTP into serotonin until it reaches the brain.[citation needed]
References[edit]
- ^ Gilbert JA, Frederick LM, Ames MM (November 2000). "The aromatic-L-amino acid decarboxylase inhibitor carbidopa is selectively cytotoxic to human pulmonary carcinoid and small cell lung carcinoma cells". Clinical cancer research : an official journal of the American Association for Cancer Research 6 (11): 4365–72. PMID 11106255.
- ^ Gustafsson BI, Tømmerås K, Nordrum I, Loennechen JP, Brunsvik A, Solligård E, Fossmark R, Bakke I, Syversen U, Waldum H (March 2005). "Long-term serotonin administration induces heart valve disease in rats". Circulation 111 (12): 1517–22. doi:10.1161/01.CIR.0000159356.42064.48. PMID 15781732.
- ^ Xu J, Jian B, Chu R, Lu Z, Li Q, Dunlop J, Rosenzweig-Lipson S, McGonigle P, Levy RJ, Liang B (December 2002). "Serotonin mechanisms in heart valve disease II: the 5-HT2 receptor and its signaling pathway in aortic valve interstitial cells". Am. J. Pathol. 161 (6): 2209–18. doi:10.1016/S0002-9440(10)64497-5. PMC 1850896. PMID 12466135.
- ^ http://www.truestarhealth.com/Notes/1339004.html
External links[edit]
- Lodosyn prescribing information
- Sinemet datasheet for New Zealand
|
|||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||
UpToDate Contents
全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.
- 1. パーキンソン病の薬理学的治療 pharmacologic treatment of parkinson disease
- 2. パーキンソン病における症状の変動およびジスキネジア motor fluctuations and dyskinesia in parkinson disease
- 3. 妊娠中および授乳中のむずむず脚症候群／Willis-Ekbom病 restless legs syndrome willis ekbom disease during pregnancy and lactation
- 4. 特発性浮腫 idiopathic edema
- 5. 前頭側頭型認知症：治療 frontotemporal dementia treatment
English Journal
- Interim analysis of long-term intraduodenal levodopa infusion in advanced Parkinson disease.
- Pålhagen SE, Dizdar N, Hauge T, Holmberg B, Jansson R, Linder J, Nyholm D, Sydow O, Wainwright M, Widner H, Johansson A.SourceDepartment of Neurology, Karolinska University Hospital, Stockholm, Sweden.
- Acta neurologica Scandinavica.Acta Neurol Scand.2012 Dec;126(6):e29-33. doi: 10.1111/j.1600-0404.2012.01689.x. Epub 2012 Jun 12.
- BACKGROUND: This interim 12-month analysis is a part of an open-label, observational, prospective study on health outcomes and cost impact of levodopa/carbidopa intestinal gel (LCIG, Duodopa) in Parkinson disease (PD). The specific aim was to investigate clinical and health-related quality of life (
- PMID 22690905
- Identification of old drugs as potential inhibitors of HIV-1 integrase - human LEDGF/p75 interaction via molecular docking.
- Hu G, Li X, Sun X, Lu W, Liu G, Huang J, Shen X, Tang Y.SourceShanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
- Journal of molecular modeling.J Mol Model.2012 Dec;18(12):4995-5003. doi: 10.1007/s00894-012-1494-0. Epub 2012 Jun 26.
- Integration of viral-DNA into host chromosome mediated by the viral protein HIV-1 integrase (IN) is an essential step in the HIV-1 life cycle. In this process, human protein Lens epithelium-derived growth factor (LEDGF/p75) is discovered to function as a cellular co-factor for integration. LEDGF/p75
- PMID 22733274
Japanese Journal
- Kinetic Characterization of the Oxidation of Carbidopa and Benserazide by Tyrosinase and Peroxidase
- Munoz-Munoz Joseph Louis,Garcia-Molina Francis,Garcia-Molina Mary [他],TUDELA Joseph,GARCIA-CANOVAS Francis,RODRIGUEZ-LOPEZ Joseph Neptune
- Bioscience, biotechnology, and biochemistry 73(6), 1308-1313, 2009-06-23
- … Carbidopa and benserazide have been described as inhibitors of dopa decarboxylase and both have been used in the treatment of Parkinson's disease. …
- NAID 10027542193
- Simultaneous Kinetic-Spectrofluorometric Determination of Levodopa and Carbidopa Using Partial Least-Squares Regression
- Pagani Ariana P.,Cabezon Miguel A.,Ibanez Gabriela A.
- Analytical sciences : the international journal of the Japan Society for Analytical Chemistry 25(5), 633-638, 2009-05-10
- NAID 10025212253
- パーキンソン病の幻視・体感幻覚に抑肝散で臨床的な改善がみられた症例(神経内科学教室岩田誠教授退任記念特別号)
- 猪瀬 悠理,小林 正樹,飯嶋 睦 [他],清水 優子,内山 真一郎,岩田 誠,INOSE Yuri,KOBAYASHI Masaki,IIJIMA Mutsumi,SHIMIZU Yuko,UCHIYAMA Shinichiro,IWATA Makoto
- 東京女子医科大学雑誌 78(臨時増刊号), E203-E206, 2008-02-25
- … She has been taking levodopa/carbidopa, pergolide and cabergoline. …
- NAID 110007524809
Related Pictures
★リンクテーブル★
| リンク元 | 「カルビドパ」 |