Parkinson's medication

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Parkinson's drugs or anti- Parkinson drugs are drugs that are used to treat Parkinson's disease . Parkinson's disease is characterized by a lack of dopamine , which is caused by the death of dopaminergic nerve cells in the basal ganglia of the brain. Together with acetylcholine , serotonin and norepinephrine, dopamine is responsible for the correct transmission of motor information. If dopamine is missing, there is a relative excess of acetylcholine as well as a serotonin and norepinephrine deficiency: The movement of any muscle desired by the brain is not carried out or is carried out incorrectly and / or it moves independently.

The following options are available for treating Parkinson's disease: supplying the brain with dopamine (L-Dopa) and active ingredients that act like dopamine (dopamine agonists), inhibiting the breakdown of dopamine (COMT, MAO-B, NMDA inhibitors ) and eliminate the relative acetylcholine excess (anticholinergics). These possibilities are used in combination, either through the administration of the individual remedies or a combination preparation.

Points of attack of the Parkinson's drugs

L-dopa

Administering the missing dopamine as a medication does not achieve the goal because it can not cross the blood-brain barrier . However, this is possible with the dopamine precursor ( prodrug ) L-Dopa , for which there is an active transporter in the blood-brain barrier that transports it into the brain. There, L-Dopa is converted into dopamine by the enzyme DOPA decarboxylase, with CO 2 being split off. Since the enzyme DOPA decarboxylase is also found in the periphery outside the brain, more than 90 percent of L-Dopa would be converted into dopamine before it reached the brain if administered alone. For this reason, it is always combined with one of the two decarboxylase blockers carbidopa or benserazide , which also significantly reduce the peripheral side effects of dopamine, but in turn do not cross the blood-brain barrier.

L-Dopa is the most effective Parkinson’s drug; but it is not able to influence the progression of the disease. On the other hand, it is certain that the introduction of L-Dopa therapy has significantly increased the life expectancy of Parkinson's patients by avoiding disease-related complications. L-Dopa only remains fully effective for three to five years. After that, most patients experience fluctuations, ie fluctuations in effect. Characteristic in the affected patients is the sudden change from good mobility to immobility (on-off phenomenon). Examples of L-dopa / decarboxylase inhibitor combinations:

  • L-Dopa / Benserazid ( Madopar ® , Restex ®, etc.)
  • L-Dopa / Carbidopa ( Isicom ® , Nacom ®, etc.)

Treatment with L-Dopa was developed by George Cotzias in 1968 .

Dopamine agonists

Dopamine agonists work by stimulating dopamine receptors. While in the past they were mainly used together with L-Dopa in the advanced stage, today they are often used in the early stages as monotherapy instead of L-Dopa . There is some evidence that this may slow the disease progression, but there is insufficient evidence. The dopamine agonists differ in their pharmacokinetic properties, in their affinity for the dopamine receptor and in their intrinsic activity . There are two groups.

Dopamine agonists with an ergoline structure

The dopamine agonists in this group are derived from ergoline , the basic structure of ergot alkaloids . Examples include bromocriptine (Pravidel ® , etc.) ., Α- dihydroergocryptine (Almirid ® , Cripar ® ) , cabergoline (Cabaseril ® and others) , lisuride (DOPERGIN ® ) , and pergolide (Parkotil ® and others) . Cabergoline has a long half-life (65 h) and therefore only needs to be taken once a day. Fibroses on the heart valves are known, albeit rare, complications of long-term therapy with most of the active ingredients in this group.

Dopamine agonists without an ergoline structure

The following dopamine agonists are not chemically derived from ergoline:

Apomorphine (Dacepton ® , Apo-go ® ) , pramipexole (Sifrol ® ) , piribedil (Clarium ® ) , ropinirole (Requip ® , Adartel ® ) , and rotigotine (Neupro ® ) .

If you experience daytime sleepiness, especially with ropinirole and pramipexole, you can consider switching to a preparation from the aforementioned group.

COMT inhibitors

This group of substances includes the active substances entacapone (Comtess ® ) and tolcapone (Tasmar ® ) . By blocking the enzyme catechol-O-methyl transferase which is methylation of L-Dopa and dopamine in an ineffective metabolites prevented. Due to this mechanism of action, the sole administration of COMT inhibitors is ineffective; they must always be taken together with L-Dopa. Tolcapone has not been on the market for years because of fatal liver damage. Although it has been re-approved, it may only be used with regular liver function monitoring and when all other anti-Parkinson’s drugs are ineffective.

MAO-B inhibitors

Another way to increase the dopamine concentration in the brain is to suppress dopamine breakdown by inhibiting monoamine oxidase B (MAO-B). The two active ingredients selegiline ( Antiparkin ® , Jutagilin ® , Movergan ® and others) and rasagiline (Azilect ® ) are suitable for this. Since the enzyme blockade is irreversible, both substances work for 1 to 3 days despite their short half-life (approx. 1 hour). They are usually used in combination with L-Dopa. Both should not be taken with other MAOIs , serotonin reuptake inhibitors , serotonin agonists, or opioid analgesics. Safinamide is also said to act mainly via a (in this case reversible) MAO-B inhibition . However, other mechanisms of action are also discussed.

NMDA inhibitors (N-methyl-D-aspartate antagonists)

Amantadine ( PK-Merz et al.) Was originally developed as a flu prophylactic. It has been used for decades in Parkinson's disease in milder cases as monotherapy, otherwise in combination with other anti-Parkinson drugs. Its mechanism of action, the NMDA receptor antagonism, was only discovered a few years ago. However, it is disputed whether this is the main mechanism of action.

Budipin ( Parkinsan ) occupies an intermediate position, as it has both NMDA-antagonistic and anticholinergic mechanisms of action. Due to its QT- prolonging side effect, close heart controls are necessary. The breakdown of this active ingredient via the liver enzyme CYP 2D6 makes it susceptible to interactions , especially with metoprolol and macrolide antibiotics .

Anticholinergics

Anticholinergics are the oldest anti-Parkinson drugs. They are since 1860, at that time in the form of Belladonna - alkaloids used. They develop their effect by blocking the m- choline receptor. Approved for the Parkinson therapy biperiden ( Akineton etc.), bornaprine ( Sormodren ), metixen ( Tremarit ) and trihexyphenidyl ( Artane , Parkopan ). There does not seem to be any significant difference between these four active ingredients. The most tried and tested are Biperiden, Bornaprine and Metixen. They are used especially when Parkinson's disease is accompanied by resting tremor . Another approved antiparkinsonian drug with anticholinergic effects is procyclidine (for example as Osnervan ).


Combination preparation

A combination preparation with the active ingredients L-Dopa, Carbidopa and Entacapone is available under the trade name Stalevo . It makes it easier to take because the patient only has to deal with one type of tablet. But the proportions of L-dopa / carbidopa and entacapone can only be varied when taken separately.

literature

  • Ernst Mutschler, Gerd Geisslinger, Heyo K. Kroemer, Peter Ruth, Monika Schäfer-Korting: drug effects. Textbook of pharmacology and toxicology. 9th edition. Wissenschaftliche Verlagsgesellschaft, Stuttgart 2008, ISBN 3-80-471952-X .
  • Klaus Aktories, U. Förstermann, F. Hofmann, Klaus Starke, W. Forth, D. Henschler, W. Rummel: General and Special Pharmacology and Toxicology. 9th edition. Urban & Fischer, Munich 2006, ISBN 978-3437444906 .

Web links

Individual evidence

  1. ^ DocCheck Flexikon: Procyclidin .