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

• Dopamine agonists
• Anticholinergic drugs

In what way does amantadine act as anti-parkinsonism drug?

• Amantadine is a metaffinoid potentiator of dopamine. This means that amantadine:

• Increases release of dopamine
• Increases synthesis of dopamine
• Block reuptake of dopamine

• Amantadine also acts as NMDA antagonist which results in the anti-dyskinetic effect.
• Amantadine is an adenosine A₂ antagonist – adenosine inhibits D₂ function
• Amantadine improves rigidity, tremors and bradykinesia.

Discuss the mechanism of action of the anti-parkinsonism drugs that indirectly increase dopamine concentration.

Selective MAO-B inhibitors

• MAO-B preference for DA as substrate 
• This increases DA concentration in CNS

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

• Ergot derivatives

• Bromocriptine

• Non ergot derivatives:

• Pramipexole
• Ropinirole

List the specific dopamine receptors that are stimulated by each agonist

• Bromocriptine: partial agonist on D₂ receptors
• Pramipexole: D₃ receptors
• Ropinirole: D₂ receptors

Which of these drugs are classified as neuron protecting drugs? What does this mean?

• Pramipexole
• Decreases disease progression and affective symptoms

What is the importance of MAO-B selective drugs in the treatment of Parkinsonism?

• MAO-B has preference for DA as substrate
• This causes an increase in Dopamine in the central nervous system

How do the COMT inhibitors act in Parkinsonism?

• COMT metabolizes l-dopa to 3-O-methyl dopa (3OMD)
• 3OMD competes with l-dopa for active transport processes which causes increased plasma levels of 3OMD and weak therapeutic response with l-dopa
• COMT-inhibitors extend the duration of action of l-dopa and decreases peripheral metabolism which results in an improved bio-availability

How does Istradefyllin act?

• Istradefyllin is an adenosine A_2A antagonist
• Adenosine inhibits Dopamine 2 receptor function
• By inhibiting adenosine, it will prevent the inhibition of dopamine functions

Discuss the MOA of Safinamide

• Novel dual Mechanism of action
• Increases dopamine activity

• Potent reversible inhibition of MAO-B
• Inhibition of dopamine uptake

• Decreases glutamate release.

Source

Brand, L. 2021. Parkinson’s Disease. Study unit 8 [PowerPoint Presentation]. Unpublished lecture notes on eFundi, FKLG312. Potchefstroom: NWU.