Benserazide

Benserazide
Clinical data
Other names	Serazide, RO 4-4602
AHFS/Drugs.com	International Drug Names
Pregnancy; category	AU: B3; ;
ATC code	None;
Identifiers
	IUPAC name (RS)-2-Amino-3-hydroxy-N′-(2,3,4-trihydroxybenzyl)propanehydrazide;
CAS Number	322-35-0 ; as HCl: 14919-77-8;
PubChem CID	2327;
IUPHAR/BPS	5150;
DrugBank	DB12783; as HCl: DBSALT002687;
ChemSpider	2237 ; as HCl: 25109;
UNII	762OS3ZEJU; as HCl: B66E5RK36Q;
KEGG	D03082 ;
ChEBI	CHEBI:64187; as HCl: CHEBI:31262;
ChEMBL	ChEMBL1096979 ; as HCl: ChEMBL1255778;
CompTox Dashboard (EPA)	DTXSID9022651 ;
Chemical and physical data
Formula	C10H15N3O5
Molar mass	257.246 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES NC(CO)C(=O)NNCC1=C(O)C(O)=C(O)C=C1;
	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 ; ; as HCl: InChI=1S/C10H15N3O5.ClH/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);1H; Key:ULFCBIUXQQYDEI-UHFFFAOYSA-N;
	(verify)

Benserazide is a peripherally acting aromatic L-amino acid decarboxylase or DOPA decarboxylase inhibitor, which is unable to cross the blood–brain barrier.^[1]

It is on the World Health Organization's List of Essential Medicines.^[2]

Medical uses

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.^[3]

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. Other side effects in combination with L-DOPA include nausea, vomiting etc.^[4]

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.
^ World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
^ Ryan, Melody; Slevin, John T. (2006). "Restless legs syndrome". American Journal of Health-System Pharmacy. 63 (17): 1599-1612. Retrieved on 2008-02-06.
^ Davies, John A. (2007-01-01), Enna, S. J.; Bylund, David B. (eds.), "Benserazide", xPharm: The Comprehensive Pharmacology Reference, New York: Elsevier, pp. 1–4, doi:10.1016/b978-008055232-3.61292-9, ISBN 978-0-08-055232-3, retrieved 2024-08-25

[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.

[WHO22nd-2] World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.

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

[4] Davies, John A. (2007-01-01), Enna, S. J.; Bylund, David B. (eds.), "Benserazide", xPharm: The Comprehensive Pharmacology Reference, New York: Elsevier, pp. 1–4, doi:10.1016/b978-008055232-3.61292-9, ISBN 978-0-08-055232-3, retrieved 2024-08-25

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