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Decarboxylase inhibitors

15th of januari 2019

Last summer I went to the pharmacy for a repeat prescription for levodopa-carbidopa and, because of shortages of medication, I left with levodopa-benserazide. The difference is in the decarboxylase inhibitor.

Why does a patient get levodopa anyway? He has a shortage of dopamine, right?
That’s right. However, if you take dopamine, then it doesn’t benefit you because dopamine does not get through the blood-brain barrier (BBB). Levodopa (also called L-DOPA) is a precursor of dopamine and cán pass through the BBB. Once in the brain, it breaks down into the much-needed dopamine.

How does levodopa pass through the blood-brain barrier?

Levodopa is an amino acid, a compound with both a carboxyl group (-COOH) and an amine group (-NH2). Amino acids can use special amino acid transport systems (1) waiting for them in the BBB. Levodopa is allowed to go on transport and dopamine isn’t.

How are decarboxylase inhibitors beneficial?

The challenge is to get as much levodopa as possible intact to the BBB. The path from the ingestion of levodopa, through the stomach, the bloodstream to the brain, is covered with substances that degrade levodopa. One of those substances is Dopa Decarboxylase (DDC). DDC removes the carboxyl group of levodopa and thus it – prematurely – transforms into dopamine. By adding so-called decarboxylase inhibitors to levodopa, DDC is tricked. The inhibitors have a number of characteristics in common with levodopa. At least they are look-a-likes enough to be able to attach themselves to DDC and to divert its attention from levodopa. This allows more levodopa to flow unhindered to the BBB where its transport patiently waits.

Sparks  

Sources

(1) Barar. J., Rafi, M.A, Pourseif, M., Omidi, Y., (2016), Blood-brain barrier transport machineries and targeted therapy of brain diseases. Bioimpacts, 6(4):225-248. Retrieved from http://doi.org/10.15171/bi.2016.30

(2) Burkhard, P., Dominici, P., Borri-Voltattorni, C., Jansonius, J. N., & Malashkevich, V. N. (2001). Structural insight into Parkinson’s disease treatment from drug-inhibited DOPA decarboxylase. Nature Structural Biology, 8(11), 963–967. Retrieved from http://doi.org/10.1038/nsb1101-963

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