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

• Drugs that increase dopaminergic activity.
• Drugs that decrease cholinergic activity.

• In what way does amantadine act as a antiparkinsonism drug?

• Metaffinoid potentiator of DA (↑ in DA activity)

-  ↑ DA release

-  ↑ DA synthesis

-  Blocks reuptake of DA

• NMDA antagonist (anti-dyskinetic effects)
• Adenosine A2a Antagonist

-  Adenosine Inhibits D2 receptors.\By blocking the adenosine receptor, improve D2 function.

Improved rigidity, tremors, bradykinesia.

• Discuss the mechanisms of action of the antiparkinsonism drugs that indirectly increase dopamine concentration.

These drugs do not require enzymatic conversion to an active metabolite. They do not act directly on the post synaptic dopamine receptors. They have no potentially toxic metabolites. 

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

• Pramipexole
• Pergolide
• Bromocriptine
  • Non ergot derivative:
    • • Ropinirole
      • Rotigotine

• List the specific dopamine receptors that are stimulated by each agonist.

• Pramipexole: D3
• Ropinirole: D2
• Rotigotine: D1, D2 and D3
• Bromocriptine: D2
• Pergolide: D1 and D2

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

• MAO- B inhibitor: Rasagiline 
• This means it increases the DA stores in neurons.

• What is the importance of monoamine oxidase B (MAO-B) selective drugs in the treatment of Parkinsonism?

They work adjunctive to Levodopa. MAO-B inhibitors prolong duration of effect of levodopa. Therefore should be used with caution.

• How do the COMT-inhibitors act in Parkinsonism?

COMT metabolises L-dopa to 3-OMD. Increased plasma levels of 3OMD leads to a weak therapeutic response with L-dopa.

3-OMD competes with L-dopa for active transport.

• How does istradephyline act?

Inhibits D2 function, thus by antagonising adenosine, prevent its inhibition of dopamine function. Add on therapy to L-dopa/carbidopa experiencing on-off episodes.

• Discuss the MOA of safinamide

MOA: Novel dual MOA

1. ↑ DA activity
   • -  Potent reversible inhibition of MAO-B
   • -  Inhibition of DA uptake
2. ↓ Glutamate release

Reference list:

Brand, L.Prof.  2021.  Study Unit 8: Parkinsonism.  Unpublished lecture notes on efundi, FKLG 312.  Potchefstroom: NWU.  [PowerPoint presentation].