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

The 2 main groups of drugs that can be used to treat Parkinson’s are

- Drugs that increase dopaminergic activities

- Drugs that decrease cholinergic activities

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

Amantadine acts as an anti-parkinson’s drug by the following mechanisms:

- This drug is a Metaffinoid potentiater of DA. Thus, it increases DA release, it increases DA synthesis and blocks the reuptake of DA.

- It is a NMDA antagonist that results in anti-dyskinetic effects.

- Amantadine is an Adenosine alpha-2 antagonist. It works as an anti-viral drug that inhibits the D2 receptor function.

Amantadine improves rigidity, tremors, and bradykinesia.

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

Drugs that indirectly increase the Dopamine concentration do not require enzymatic conversion to an active metabolite. These drugs also do not act directly on the post synaptic dopamine receptors. These drugs also do not have any potentially toxic active metabolites.

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

The ergot derivatives are:

- Pramipexole

- Pergolide

- Bromocriptine

Non-ergot derivatives:

- Ropinirole

- Rotigotine

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

Dopamine 3 = Pramipexole

Dopamine 2 = Ropinirole

Dopamine 1,2 and 3 = Rotigotine

Dopamine 2 = Bromocriptine

Dopamine 1 and 2 = Pergolide

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

MAO-B inhibitors such as Rasagiline and Selegiline are classified as neuro protective drugs. This means that the Dopamine concentration levels in the central nervous system are increased.

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

These drugs work with drugs such as Levodopa. MAO-B inhibitors prolong the duration of the effects of Levodopa.

• How do the COMT-inhibitors act in Parkinsonism?

COMT inhibitors metabolize L-dopa to 3-O-methyl dopa (30MD), the increased levels of 3OMD leads to a weak therapeutic response with L-dopa. 30MD competes with L-dopa for active transport processes. These drugs increase the duration of L-dopa thus, decreasing peripheral metabolism and improving bioavailability of the drug.

• How does istradephyline act?

This drug inhibits Dopamine 2 functioning by antagonising adenosine activity preventing the inhibition of dopamine functions. It is an additional therapy to L-dopa or carbidopa therapy that experiences on-off episodes.

• Discuss the MOA of safinamide

Safinamide, increases DA activity, this results in the potent reversible inhibition of MAO-B and results in the inhibition of DA reuptake. This drug also results in the decrease of glutamate release.

Brand, L. 2021. Parkinsonism. Unpublished Lecture notes on eFundi. [PowerPoint Presentation]. Study Unit 8, FKLG 312. Potchefstroom, NWU.