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 ;
PubChem CID	2327;
IUPHAR/BPS	5150;
ChemSpider	2237 ;
UNII	B66E5RK36Q;
KEGG	D03082 ;
ChEMBL	ChEMBL1096979 ;
CompTox Dashboard (EPA)	DTXSID9022651 ;
Chemical and physical data
Formula	C10H15N3O5
Molar mass	257.246 g·mol−1
3D model (JSmol)	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) ; Key:BNQDCRGUHNALGH-UHFFFAOYSA-N ;
	(verify)

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.[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 leg 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 cannot cross the blood–brain barrier itself, 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 levodopa 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.

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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.

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[pmid12703659-1] 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.

[2] Ryan, Melody; Slevin, John T. (2006). "Restless legs syndrome". American Journal of Health-System Pharmacy. 63 (17): 1599-1612. Retrieved on 2008-02-06.