• Which two main groups of drugs are important in the treatment of Parkinsonism?
  • Drugs that increase Dopamine Activity which are L-dopa and dopamine agonists
  • Drugs that decrease Anti-cholinergic Activity, Anti cholinergic drugs

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

It acts as a Metaffinoid potentiator of DA. It increases DA release & synthesis and Block DA reuptake. Its further acts as an adenosine A2 Antagonist as well as an NMDA Antagonist.

• Discuss the mechanisms of action of the antiparkinsonism drugs that indirectly increase dopamine concentration.
  • MAO-B Inhibitors. These drugs work to increase extracellular Dopamine levels in the striatum by suppressing metabolism of dopamine.
  • COMT-Inhibitors. These work to inhibit COMT in the periphery therefore decreasing peripheral metabolism as it inhibits the formation of 3-OMD, in turn increase the concentration of dopamine in the brain.

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

Bromocriptine: ergot derivative

Pramipexole & Ropinirole:  not ergot derivatives

• List the specific dopamine receptors that are stimulated by each agonist.
  • Bromocriptine and Ropinirole: D2 Agonist
  • Pramipexole: D3 Agonist

• Which of these drugs are classified as neuron protecting drugs?  What does this mean?
  • Pramipexole is known as neuroprotective – delay disease progression prevents the degeneration of dopamine neurons due to constant stimulation

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

Allow for Dopamine neurons to be constantly stimulated without allowing for degeneration as they are neuroprotective.

• How do the COMT-inhibitors act in Parkinsonism?

These drugs extend the action of L-dopa by decreasing the peripheral metabolism and increasing the bioavailability of dopamine in the brain and inhibiting the formation of the 3-OMD metabolite.

• How does istradephyline act?

It functions as an adenosine A_2A Antagonist by blocking the adenosine receptor, improve D2 function & also acts as an antiviral

• Discuss the MOA of safinamide

Has a Dual MOA:

Increases DA activity as it is a potent reversible MAO-B inhibitor and inhibits DA reuptake.

Decrease Glutamate release

Brand, L. 2021. Parkinsonism & other movement disorders. SU. 8 [PowerPoint Presentation]. Unpublished Lecture Notes on eFundi, FKLG 312. Potchefstroom, NWU.

Katzung, B.G. 2018. Basic and Clinical Pharmacology. 14^th ed. United States of America: McGraw-Hill Education