BLOG #10

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

Dopamine agonists and anticholinergic 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 dopamine agonists are ergot derivatives and which are not?

Ergot derivatives: Bromocriptine

Non-ergot derivatives: Pramipexole and Ropinirole

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

D2 receptor agonists:

-Ropinirole

-Bromocriptine

D3 receptor agonists:

-Pramipexole

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

Selective Monoamine Oxidase B (MAO-B) inhibitors (eg Rasagiline). This means that the MAO-B inhibitor prevents MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) from being converted to MPP + (N-methyl-4-phenylpyridium), which can therefore protect against the prevalence of Parkinsonism.

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

These drugs work with drugs such as Levodopa. MAO-B inhibitors prolong the duration of the effects of Levodopa.

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

COMT inhibitors metabolize L-dopa to 3-O-methyl dopa (30MD), the increased levels of 3OMD leads to a weak therapeutic response with L-dopa. 30MD competes with L-dopa for active transport processes. These drugs increase the duration of L-dopa thus, decreasing peripheral metabolism and improving the bioavailability of the drug.

9. How does Istradephyline act?

This drug inhibits Dopamine 2 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.