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

Drugs that increase dopamine activity thus Dopamine agonist like Pramipexole and drugs that would decrease the cholinergic levels to restore the imbalance implicated by this disease, thus anticholinergic drugs.

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

Amantadine is a metaffiniod potentiator of dopamine which means that it will increase dopamine activity by increasing dopamine release, increasing the synthesis of dopamine, and blocking the reuptake of dopamine.

It is however classified as a NMDA antagonist; thus, it has anti-dyskinetic properties.

It also has the ability to act as an adenosine A2a antagonist, contributing to antiviral effects.

This broad mechanism of action gives amantadine the ability to improve bradykinesia, tremors, and rigidity, associated with parkinsonism.

Unfortunately, this drug only works for a few weeks.

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

MOA B inhibitors (Rasagiline and Selegiline): Inhibits MOA which is the enzyme responsible for the metabolism of dopamine. Therefore, increasing dopamine levels.

COMT inhibitor (Entacapone): Extends the duration of action of l-dopa by decreasing peripheral metabolism and increasing its bioavailability.

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

Ergot derivatives: Bromocriptine

Non-ergot derivatives: Ropinirole and Pramipexole

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

Pramipexole – direct agonist on D3 receptors

Ropinirole- D2 agonist

Bromocriptine – Partial agonist on D2

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

Selegiline and Rasagiline has been said to have neuroprotective properties by preventing the metabolism of dopamine it ensures that the dopamine neurons are stimulated.

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

It prevents the metabolism of dopamine thus increasing the dopamine levels and ensuring that the dopamine neurons are stimulated continuously.

• How do the COMT-inhibitors act in Parkinsonism?

COMT metabolises L-dopa to 3OMD. Where increased levels of 3OMD has a weak therapeutic response with L-dopa due to them competing for active transport, thus it increases the duration of action of L-dopa by decreasing peripheral metabolism and increasing it bioavailability.

• How does istradephyline act?

It acts as Adenosine a_2A  antagonist. Adenosine is known to block dopamine 2 receptors thus blockade of adenosine improves dopamine 2 function.

• Discuss the MOA of safinamide

MOA: Noval dual MOA where it increases dopamine activity by causing reversible inhibition of MAO-B. Inhibition of DA uptake decreases glutamate release.