1. Which two main groups of drugs are important in the treatment of Parkinsonism?

• Drugs that promote increased dopamine activity.
• Agents that promote reduced anticholinergic activity.

2. How does amantadine act as an antiparkinsonian agent?

Amantadine is an antiviral drug with a broad mechanism of action. It is a metaffinoid potentiator of dopamine. It increases the synthesis and release of dopamine. It also blocks the reuptake of dopamine NMDA antagonist. It only improves rigidity, tremors and bradykinesis and is only effective for a few weeks.

3. Discuss the mechanisms of action of the antiparkinsonian drugs that indirectly increase dopamine concentration.

The mechanism of action of antiparkinsonian drugs that indirectly increase dopamine concentration is explained as follows:

Amantadien:

• Metaffinoid potentiator of DA
• ↑ exemption from DA
• ↑ synthesis of DA
• Block DA re-admission

Selective MAO-B inhibitors:

• MAO B preference for DA as substrate
• ↑ DA concentration in SSS

Safinamide:

• ↑ DA activity

• Inhibition of DA re-admission

4. Which of the dopamine agonists are ergot derivatives and which are not?

Bromocriptine = ergot derivative

Pramipexole = not ergot derivative

Ropinirole = not ergot derivative

Rotigotine = not ergot derivative

5. Make a list of the specific dopamine receptors that are stimulated by each agonist.

Bromocriptine: partial agonist at D2 receptors

Pramipexole: affinity for D3 receptor family

Ropinirole: D2 agonist

Rotigotine: D1; D2 and D3 receptors

6. Which of these drugs are classified as neuronal protective drugs? What does it mean?

Substances that can be classified as neuronal protective agents are the MAO inhibitors such as Selegiline and Rasagiline. These drugs therefore increase the dopamine concentration in the central nervous system and suppress the metabolism of dopamine.

7. What is the importance of Monoamine Oxidase B (MAO-B) selective drugs in the treatment of Parkinsonism?

• MAO B preference for DA as substrate
• ↑ DA concentration in SSS
• Neuronutrients, ↓ disease progression
• AI: Pethidine, tramadol, SSRIs, OTC cold preparations, liver dysfunction

8. How do the COMT inhibitors work in Parkinsonism?

• COMT metabolizes l-dopa to 3-O-methyl dopa (3OMD).
• Elevated plasma levels of 3OMD poor therapeutic response with l-dopa (3OMD competes with l-dopa for active transport processes).
• COMT inhibitor prolongs the duration of action of l-dopa, ↓ peripheral metabolism, improved bioavailability.
• Additional drugs with l-dopa, improved response and prolonged on-time.
• Stalevo® Entacapone, l-dopa, carbidopa combination.

9. How does Istradephilin work?

This drug is a selective adenosine A2A receptor antagonist that targets these receptors found in the basal ganglia. This drug stimulates the central nervous system and can show improved motor function. In combination with L-dopa, dopamine activity is increased by this drug by antagonizing adenosine in the basal ganglia.

10. Discuss the mechanism of action of safinamide

This remedy has a dual mechanism of action.

1. Increases dopamine activity. Potent reversible inhibition of MAO-B. Inhibition of dopamine reuptake.

2. Reduce glutamate release.