1. Which two main groups of drugs are important in the treatment of parkinsonism? 

Dopamine agonists and anti-cholinergic drugs. 

 

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

Amantadine enhances dopaminergic neurotransmission by unknown mechanisms that involve increasing synthesis or release of dopamine or inhibition of dopamine reuptake. The drug also has muscarinic blocking actions. Amantadine improves bradykinesia, rigidity, and tremor. It also has antiviral effects. 

 

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

Monoamine Oxidase Inhibitors ( Selegiline and Rasagiline): These are selective inhibitors of monoamine oxidase type B, the form of the enzyme that metabolizes dopamine. This indirectly increases dopamine concentrations by preventing its metabolism. Hepatic metabolism of Selegiline results in the formation of desmethylselegiline (neuroprotective) and amphetamine. 

Catechol-O-methyltransferase Inhibitors (Entacapone and Tolcapone): COMT is the enzyme that converts Levodopa to 3-O-methyldopa. These drugs inhibit COMT, thereby increasing the concentration of Levodopa. 

Amantadine: this drug inhibits the reuptake of dopamine, thereby indirectly increasing the concentration of dopamine. 

 

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

Ergot alkaloids: Bromocriptine

Non Ergot alkaloids: Pramipexole and Ropinirole. 

 

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

Pramipexole: D3 receptors

Bromocriptine and Ropinirole: D2 receptors. 

 

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

The monoamine oxidase inhibiting drug Selegiline is metabolised to form desmethylselegiline and this is classified as neuroprotective. A neuroprotective drug in terms of Parkinsonism is a drug which delays or prevents the death of dopamine producing cells in the brain, thereby slowing or halting the progression of the disease. 

 

7. What is the importance of MAO-B selective drugs in the treatment of parkinsonism?

MAO-B selective drugs are important in the treatment of parkinsonism because they inhibit the enzyme MOA-B which metabolizes dopamine. This results in an increase in dopamine levels in the body, thereby providing symptomatic relief in patients with Parkinson's. 

 

8. How do the COMT-inhibitors act in parkinsonism?

COMT inhibitors (Entacapone and Tolcapone) are useful in the treatment of Parkinsonism because they inhibit the conversion of Levodopa to 3OMD. 3OMD increased concentrations in the plasma is associated with poor response to Levodopa because it competes with Levodopa for active transport into the CNS. Therefore COMT inhibitors decrease plasma levels of 3OMD and increase the levels of Levodopa. 

 

9. How does istradefylline act?

Istradefylline is an adenosine alpha 2A receptor used to treat Parkinsonism by reducing the overactivity of the striatal pathway restoring the balance of the basal ganglia. 

 

10. Discuss the MOA of safinamide 

Safinamide is is a monoamine oxidase B inhibitor. It is used to reduce response fluctuations in patients taking Carbidopa-Levodopa, diminishing off-periods in patients with wearing-off effect or on-off phenomena. It's mechanism of action, like Rasagiline and Selegiline, it inhibits the dopamine metabolising enzyme MAO-B, thus increasing dopamine concentrations.