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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/12/10 15:06:35」(JST)

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Benserazide (also called Serazide or Ro 4-4602) is a peripherally-acting aromatic L-amino acid decarboxylase (AADC) or DOPA decarboxylase inhibitor, which is unable to cross the blood–brain barrier.^[1]

Indications

It is used in the management of Parkinson's disease in combination with L-DOPA (levodopa) as co-beneldopa (BAN), under the brand names Madopar in the UK and Prolopa in Canada, both made by Roche. Benserazide is not approved for use in the US; carbidopa is used instead for the same purpose. These combinations are also used for the treatment of restless legs syndrome.^[2]

Pharmacology

Levodopa is a precursor to the neurotransmitter dopamine which is administered to increase its levels in the central nervous system. However, most levodopa is decarboxylated to dopamine before it reaches the brain, and since dopamine is unable to cross the blood–brain barrier, this translates to little therapeutic gain with strong peripheral side effects.

Benserazide inhibits the aforementioned decarboxylation, and since it itself cannot cross the blood–brain barrier, this allows dopamine to build up solely in the brain instead. Adverse effects caused by peripheral dopamine, such as vasoconstriction, nausea, and arrhythmia, are minimized. However, benserazide cannot reduce the centrally-mediated side effects of levodopa, particularly dyskinesia.

Benserazide has little therapeutic effect on its own, and its effect occurs synergically in combination with levodopa.

The enzyme inhibited by Benzerazide, catalyzes many different decarboxylations. The same effect of concentrating the conversion of l-dopa into dopamine to the central nervous system can be achieved with the following decarboxylations being confined to the central nervous system:

5-htp to serotonin
Tryptophan to Tryptamine
Phenylalanine to Phenethylamine
L-Tyrosine to Tyramine

Centrally-mediated side effects of higher levels of neuro and trace amine transmitters may worsen in combination with monoamine oxidase inhibitors.

Synthesis

Benserazide synthesis.^[3]

References

^ Shen H, Kannari K, Yamato H, Arai A, Matsunaga M (March 2003). "Effects of benserazide on L-DOPA-derived extracellular dopamine levels and aromatic L-amino acid decarboxylase activity in the striatum of 6-hydroxydopamine-lesioned rats". The Tohoku journal of experimental medicine 199 (3): 149–59. doi:10.1620/tjem.199.149. PMID 12703659.
^ Ryan, Melody; Slevin, John T. (2006). "Restless legs syndrome". American Journal of Health-System Pharmacy. 63 (17): 1599-1612. Retrieved on 2008-02-06.
^ http://drugsynthesis.blogspot.co.uk/2011/12/laboratory-synthesis-of-benserazide.html

UpToDate Contents

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1. パーキンソン病の薬理学的治療 pharmacologic treatment of parkinson disease
2. ジストニアの治療 treatment of dystonia
3. レストレスレッグ症候群 restless legs syndrome
4. 患者情報：パーキンソン病の治療選択肢・薬物療法（詳細） parkinson disease treatment options medications beyond the basics
5. ハンチントン病：管理 huntington disease management

English Journal

Effect of simvastatin on L-DOPA-induced abnormal involuntary movements of hemiparkinsonian rats.

Wang T1, Cao X, Zhang T, Shi Q, Chen Z, Tang B.
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology.Neurol Sci.2015 Aug;36(8):1397-402. doi: 10.1007/s10072-015-2127-z. Epub 2015 Mar 19.
Chronic L-3,4-dihydroxyphenylalanine (L-DOPA) treatment of Parkinson's disease (PD) often results in debilitating involuntary movements known as L-DOPA-induced dyskinesia (LID), which is the main obstacle in PD. The abnormal involuntary movements (AIMs) are consistently involved with the activation
PMID 25787808

Coadministration of hydroxysafflor yellow A with levodopa attenuates the dyskinesia.

Wang T1, Duan SJ2, Wang SY3, Lu Y3, Zhu Q3, Wang LJ2, Han B4.
Physiology & behavior.Physiol Behav.2015 Aug 1;147:193-7. doi: 10.1016/j.physbeh.2015.04.038. Epub 2015 Apr 23.
Levodopa (L-DOPA) is used as the most effective drug available for the symptomatic treatment of Parkinson's disease (PD). However, long-term treatment of L-DOPA frequently causes complications, including abnormal involuntary movements such as dyskinesia and response fluctuations in PD patients. In t
PMID 25914172

Benserazide, the first allosteric inhibitor of Coxsackievirus B3 3C protease.

Kim BK1, Cho JH2, Jeong P3, Lee Y4, Lim JJ4, Park KR4, Eom SH4, Kim YC5.
FEBS letters.FEBS Lett.2015 Jul 8;589(15):1795-801. doi: 10.1016/j.febslet.2015.05.027. Epub 2015 May 25.
Coxsackievirus B3 is the main cause of human viral myocarditis and cardiomyopathy. Virally encoded Coxsackievirus 3C protease (3C(pro)) plays an essential role in viral proliferation. Here, benserazide was discovered as a novel inhibitor from a drug library screen targeting Coxsackievirus 3C(pro) us
PMID 26022398

Japanese Journal

Beneficial antioxidant properties of betaine against oxidative stress mediated by levodopa/benserazide in the brain of rats

Alirezaei Masoud,Khoshdel Zeynab,Dezfoulian Omid [他]
The journal of physiological sciences 65(3), 243-252, 2015-05
NAID 40020443955

Combined Low Calcium and Lack Magnesium Is a Risk Factor for Motor Deficit in Mice

TANIGUCHI Ryoo,NAKAGAWASAI Osamu,TAN-NO Koichi [他],YAMADERA Fumihiro,NEMOTO Wataru,SATO Shoko,YAOITA Fukie,TADANO Takeshi
Bioscience, biotechnology, and biochemistry 77(2), 266-270, 2013-02-23
… LCa/Mg diet-induced catalepsy was improved by the administration of L-DOPA (50–200 mg/kg i.p.) in combination with benserazide (25 mg/kg i.p.), or of bromocriptine (0.25–4 mg/kg i.p.) or of amantadine (5–20 mg/kg i.p.). …
NAID 10031164726

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

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★リンクテーブル★

リンク元	「ベンセラジド」
拡張検索	「benserazide hydrochloride」

「ベンセラジド」

Benserazide
Systematic (IUPAC) name
	(RS)-2-amino-3-hydroxy-N′-(2,3,4-trihydroxybenzyl)propanehydrazide
Clinical data
AHFS/Drugs.com	International Drug Names
Pregnancy; category	AU: B3; ;
Legal status	UK: POM (Prescription only); (with levodopa);
Pharmacokinetic data
Excretion	Renal and fecal
Identifiers
CAS Number	14919-77-8
PubChem	CID: 2327
IUPHAR/BPS	5150
ChemSpider	2237
UNII	B66E5RK36Q
KEGG	D03082
ChEMBL	CHEMBL1096979
Chemical data
Formula	C10H15N3O5
Molecular mass	257.243 g/mol
	SMILES O=C(NNCc1c(O)c(O)c(O)cc1)C(N)CO ;
	InChI InChI=1S/C10H15N3O5/c11-6(4-14)10(18)13-12-3-5-1-2-7(15)9(17)8(5)16/h1-2,6,12,14-17H,3-4,11H2,(H,13,18) ; Key:BNQDCRGUHNALGH-UHFFFAOYSA-N ;
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