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

• Drugs that increase DA activity
• Drugs that decrease cholinergic activity

In what way does amantadine act as an anti-parkinsonism drug?

• Amantadine is a metaffinoid potentiator of DA therefore it increases the DA activity. 

Discuss the mechanisms of action of the anti-parkinsonism drugs that indirectly increase dopamine concentration.

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

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

• Ergot derivatives: Bromocriptine
• Non ergot derivative: Ropinirole and Pramipexole

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

• D1
• 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 in combination with Levodopa to treat secondary parkinsonism 

How do the COMT-inhibitors act in Parkinsonism?

• COMT metabolises L-dopa to 3OMD. Increased plasma levels of 3OMD lead to a weak therapeutic response with L-dopa (3OMD competes with L-dopa for active transport)

How does istradephyline act?

• it acts as an adenosine 2 antagonist

Discuss the MOA of safinamide

• Increases DA activity 
• Decreases glutamate release