• Which two main groups of drugs are important in the treatment of Parkinsonism?
• Drugs that increase dopamine energy activity
• Drugs that work by that lowering cholinergic activity
• In what way does amantadine act as an antiparkinsonian drug?
• Amantadine increases the release of dopamine as well as increasing its synthesis.
• It also works by blocking the reuptake of dopamine
• Amantadine is an NMDA antagonists. 
• It is also adenosine  antagonist = adenosine inhibits dopamine and thus antagonize to increase dopamine activity. 
• It improves rigidity, tremors and bradykinesia.

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

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• 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.
  • DA3 = Pramipexole
  • DA2 = Ropinirole, Bromocriptine
  • DA1,DA2 and DA3 = Rotigotine
  • DA1 and DA2 = Pergolide

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

MAO-B inhibitors (Rasagiline and Selegiline) are classified as neuro-protective drugs. This means that the DA 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?

The importance of MAO-B inhibitors is that they prolong the duration of the effects of Levodopa. 

• How do the COMT-inhibitors act in Parkinsonism?

Catechol-O-methyltransferase (COMT) Inhibitors

1. Mechanism of action:

Entacapone and tolcapone are inhibitors of COMT, the enzyme in both the CNS and peripheral

tissues that convert levodopa to 3OMD.

Increased plasma levels of 3OMD are associated with poor response to levodopa partly because the compound competes with levodopa for active transport into the CNS.

Entacapone acts only in the periphery.

• How does istradephyline act?

This drug inhibits DA2 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.