Benserazide

Benserazide
Clinical data


AHFS/Drugs.com	International Drug Names
Pregnancy category	AU: B3
Legal status
Legal status	UK: POM (Prescription only) (with levodopa)
Pharmacokinetic data
Excretion	Renal and fecal
Identifiers
IUPAC name (RS)-2-Amino-3-hydroxy-N′-(2,3,4-trihydroxybenzyl)propanehydrazide
CAS Number	14919-77-8^Y
PubChem (CID)	2327
IUPHAR/BPS	5150
ChemSpider	2237^Y
UNII	B66E5RK36Q^Y
KEGG	D03082^Y
ChEMBL	CHEMBL1096979^Y
Chemical and physical data
Formula	C₁₀H₁₅N₃O₅
Molar mass	257.243 g/mol
3D model (Jmol)	Interactive image
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)^Y Key:BNQDCRGUHNALGH-UHFFFAOYSA-N^Y
(verify)

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:

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

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.

Antiparkinson agents (N04)

Dopaminergics

DA precursors/prodrugs	Levodopa^# Melevodopa

DA receptor agonists	Apomorphine Bromocriptine Cabergoline Dihydroergocryptine Lisuride Pergolide Piribedil Pramipexole Ropinirole Rotigotine

MAO-B inhibitors	Rasagiline Selegiline

COMT inhibitors	Entacapone Tolcapone

AAAD inhibitors	Benserazide Carbidopa^#

Anticholinergics

Others

^#WHO-EM
^‡Withdrawn from market
Clinical trials:
- ^†Phase III
- ^§Never to phase III

Monoamine metabolism modulators

Common
(non-specific)

AAAD

MAO

Inhibitors: Non-selective: Benmoxin Caroxazone Echinopsidine Furazolidone Guineesine Hydralazine Indantadol Iproclozide Iproniazid Isocarboxazid Isoniazid Linezolid Mebanazine Metfendrazine Nialamide Octamoxin Paraxazone Phenelzine Pheniprazine Phenoxypropazine Pivhydrazine Procarbazine Safrazine Tranylcypromine

Inhibitors: MAO-A-selective: Amiflamine Bazinaprine Befloxatone Brofaromine Cimoxatone Clorgiline CX157 (Tyrima) Eprobemide Esuprone Harmala alkaloids (e.g., harmine, harmaline, harman, norharman, tetrahydroharmine) Methylene blue Metralindole Minaprine Moclobemide Pirlindole Sercloremine Tetrindole Toloxatone

Inhibitors: MAO-B selective: Almoxatone D-Deprenyl Ethanol Ladostigil Lazabemide Milacemide Mofegiline Nicotine Pargyline^‡ Rasagiline Safinamide Selegiline (L-Deprenyl)

Phenethylamines
(dopamine, epinephrine,
norepinephrine)

PAH	Inhibitors: 3,4-Dihydroxystyrene

TH	Inhibitors: 2-Hydroxyestradiol 2-Hydroxyestrone 3-Iodotyrosine Aquayamycin Bulbocapnine Metirosine Oudenone

DBH	Inhibitors: Bupicomide Disulfiram Dopastin Fusaric acid Nepicastat Phenopicolinic acid Tropolone

PNMT	Inhibitors: CGS-19281A SKF-64139 SKF-7698

COMT	Inhibitors: 2-Hydroxyestradiol 2-Hydroxyestrone Entacapone Nitecapone Tolcapone

Tryptamines
(serotonin, melatonin)

TPH	Inhibitors: AGN-2979 Fenclonine (PCPA) Telotristat

See also: Adrenergics • Dopaminergics • Melatonergics • Serotonergics • Monoamine reuptake and release modulators • Monoamine neurotoxins

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