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. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

Indications

It is used in the management of

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...

in combination with L-DOPA (

levodopa -DOPA, also known as levodopa and -3,4-dihydroxyphenylalanine, is an amino acid that is made and used as part of the normal biology of some plants and animals, including humans. Humans, as well as a portion of the other animals that utilize -DOPA ...

) as co-beneldopa (

BAN Ban, or BAN, may refer to: Law * Ban (law), a decree that prohibits something, sometimes a form of censorship, being denied from entering or using the place/item ** Imperial ban (''Reichsacht''), a form of outlawry in the medieval Holy Roman ...

), 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.Ryan, Melody; Slevin, John T. (2006)
"Restless legs syndrome"
''American Journal of Health-System Pharmacy''. 63 (17): 1599-1612. Retrieved on 2008-02-06.

Pharmacology

Levodopa is a precursor to the

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neur ...

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 8 ...

, which is administered to increase its levels in the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

. However, most levodopa is

decarboxylated Decarboxylation is a chemical reaction that removes a carboxyl group and releases carbon dioxide (CO2). Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is t ...

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 Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood ve ...

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

, and

arrhythmia Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...

, are minimized. However, benserazide cannot reduce the centrally mediated side effects of levodopa, particularly

dyskinesia Dyskinesia refers to a category of movement disorders that are characterized by involuntary muscle movements, including movements similar to tics or chorea and diminished voluntary movements. Dyskinesia can be anything from a slight tremor o ...

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

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...

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: * 5-HTP to serotonin *

Tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromati ...

tryptamine Tryptamine is an indolamine metabolite of the essential amino acid, tryptophan. The chemical structure is defined by an indole ─ a fused benzene and pyrrole ring, and a 2-aminoethyl group at the second carbon (third aromatic atom, with the f ...

Phenylalanine Phenylalanine (symbol Phe or F) is an essential α-amino acid with the formula . It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine. This essential amino a ...

to phenethylamine * L-tyrosine to

tyramine Tyramine ( ) (also spelled tyramin), also known under several other names, is a naturally occurring trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent. Notably, it is unable to cross the blood ...

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

References

{{Monoamine metabolism modulators Pyrogallols Hydrazides Aromatic L-amino acid decarboxylase inhibitors Antiparkinsonian agents Peripherally selective drugs