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

Increase Dopamine (DA) activity 

Decrease cholinergic activity 

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

Amantadine is known as Metaffinoid potentiator of DA and thus increase the release of DA and increase synthesis of DA and also blocks the reuptake of DA. It has antidyskinetic effects thus it acts as NMDA antagonist. It functions as Adenosine A2 antagonist so the adenosine blocks D2 receptor function ans thus it is antiviral. This way the Dopamine decreases. 

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

Amentadine: Metaffinoid potentiator of DA which increases the release of DA and also increases the synthesis of DA and further blocks the reuptake of DA. 

Selective MAO-B inhibitors: prefers dopamine as a substrate. Increases dopamine concentration in the central nervous system. The drugs can be as follows: Selegaline and Rasagiline. 

COMT inhibitors: Entacapone

COMT metabolizes l-dopa to 3-O-methyl dopa (3OMD). The increased plasma levels of 3OMD results in weak therapeutic response with l-dopa, because they compete for active processes. Furthermore, the COMT-inhibitor prolongs the duration of action of l-dopa  this way peripheral metabolism will decrease and bioavailability will thus be improved. 

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

Ergot derivatives: Bromocriptine

Non-Ergot derivatives: Pramipexole and Ropinirole. 

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

D2: Ropinirole and Bromocrptine 

D3: Pramipexole 

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

Selective monoamine inhibitors(MAO-B) inhibitors such as Rasagalinw and Selegaline. The MAO-B inhibitors does not allow the conversion MPTP to MPP which further acts as a protector and prevents neuronal/cell death. 

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

Prefers Dopamine as a subtrate therefore increases the concentration of DA in the central nervous system. 

• How do the COMT-inhibitors act in Parkinsonism? 

COMT metabolizes l-dopa to 3-O-methyl dopa (3OMD). The increased plasma levels of 3OMD results in weak therapeutic response with l-dopa, because they compete for active processes. Furthermore, the COMT-inhibitor prolongs the duration of action of l-dopa  this way peripheral metabolism will decrease and bioavailability will thus be improved. 

• How does istradephyline act?

This drug acts as Adenosine a2-A antagonist and furthere adds on therapy to l-dopa/carbidopa experiencing the Off episodes. 

• Discuss the MOA of safinamide

Safinamide consists of dual mechanism of action. This drug increases the activity of dopamine by the potent reversible inhibition of MAO-B and also the inhibition of dopamine uptake and decreases glutamate release. 

Brand, L. 2021. Parkinsonism and other movement disorders. Study unit 8 [PowerPoint Presentation]. Unpublished lecture notes on eFundi, FKLG312. Potchefstroom: NWU