Decarboxylase inhibitors

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As decarboxylase (also decarboxylase inhibitors , DDCI or DDI ( D OPA D e c arboxylase- I nhibitor )) are used in medicine pharmacological denotes agents that the enzyme DOPA decarboxylase inhibit. They are used with levodopa in the treatment of Parkinson's disease . This combination principle has been known in principle since 1960, today the administration of levodopa alone is considered obsolete, i. H. not up to date anymore.

Today five inhibitors of DOPA decarboxylase are known:

  • Benserazide - DL -Serine-2- (2,3,4-trihydroxybenzyl) hydrazide
  • Carbidopa - (-) - L - α -hydrazino-3,4-dihydroxy- α -methylhydrocinnamic acid,
  • L -Serine-2- (2,3,4-trihydroxybenzyl) hydrazide
  • Glycine 2- (2,3,4-trihydroxybenzyl) hydrazide
  • L -Tyrosine 2- (2,3,4-trihydroxybenzyl) hydrazide

Nevertheless, essentially only benserazide and carbidopa are used medicinally in various combination preparations.

Mechanism of action

Decarboxylase inhibitors block one of two ways that levodopa can be inactivated before it reaches the central nervous system, namely, its breakdown by the enzyme AADC . The second way is blocked by COMT inhibitors .

Decarboxylase inhibitors prevent the carboxy group (-COOH) of levodopa from being split off by aromatic L-amino acid decarboxylases , which are mainly found in the human body in the intestines and bloodstream.

The effect of decarboxylase inhibitors is based on two facts: on the one hand, after decarboxylation to dopamine, levodopa is no longer able to cross the blood-brain barrier and reach its target. By preventing decarboxylation before it crosses the blood-brain barrier, more levodopa reaches the central nervous system (CNS) and can take effect there. On the other hand, the inhibitors cannot get into the CNS. Thus, they only reduce the premature metabolism of levodopa in the body periphery, the desired decarboxylation in the CNS is not influenced.

Use

If levodopa is given as a single preparation, its therapeutic effect diminishes over the course of years of treatment to such an extent that even increasing the dose to the limit of tolerability is no longer beneficial. By using decarboxylase inhibitors, this effect can be significantly reduced. Therefore, single therapy with levodopa is no longer carried out today, in Germany only combination products are available.

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  1. ↑ Espacenet Patent CA1315690 (C) - 1993-04-06
  2. ^ S2 guideline of the German Society for Neurology "Parkinson's Syndromes, Diagnostics and Therapy" ( Memento from May 24, 2012 in the Internet Archive )
  3. ^ Medicines Commission of the German Medical Association: Medicinal Ordinances, 22nd edition, 2009, MMI-Verlag

Web links

Wikibooks: Decarboxylase Inhibitors  - Learning and Teaching Materials