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

1. Drugs that increase dopamine activity
2. Drugs which decrease cholinergic activity

In what way does amantadine act as a antiparkinsonism drug?

Amantadine is a metaffinoid potentiator of dopamine. The mechanism ivolves increasing the reease of DA, increasing the synthesis of DA and blocking the re-uptake of DA. An additional mechanism for antiparkinsonism activity is the antagonistic action on NMDA receptros which decreases excitatory glutamate.

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

Selective MAO-B inhibitors indirectly increases DA levels. By inhibiting monoamine-oxidase which is responsible for the metabolism of dopamine it indirectly increases the DA still available.

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

Ergot derivatives- bromocriptine

Non ergot derivative- pramipexole & ropinirole

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

Bromocriptine is a partial agonist on D₂ receptos

Pramipexole- agonist with affinity for D₃ receptors

Ropinirole- D₂ agonist

Amantadine- metaffinoid potentiater of dopamine

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

MAO-B inhibitors like Rasagiline is classified as neuron-protecting. Neuroprotection is an effect that may result in salvage, recovery or regeneration of the nervous system, its cells, structure and function. A type of prophylactic drug that can be used to prevent neurodegeneration to a certain extent.

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

MAO-B is an isomer of the MAO enzymes. MAO-B specifically has an affinity for dopamine and tyramine so this specificity creates a direct increase of dopamine by decreasing its metabolism via this pathway.

How do the COMT-inhibitors act in Parkinsonism?

COMT enzymes metabolize l-dopa (precursor of dopamine) to 3-O-methyl dopa (3OMD). By inhibiting these enzymes less 3OMD is formed and less competition for active transport into the brain between l-dopa and 30MD is achieved and thus decreased metabolism via COMT of l-dopa and less competition for transport then improves the bioavailability of l-dopa that can cross the blood brain barrier.

How does istradephyline act?

Via Adenosine A_2A antagonism thus having anticholinergic activity. D₂ function is inhibited by adenosine

Discuss the MOA of safinamide

Has a dual mechanism of action. It increases DA activity by inhibiting the re-uptake as well as being a potent reversible blocker of MAO-B. Additionally it also decreases glutamate release.

https://pubmed.ncbi.nlm.nih.gov/11749009/

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