Name of Blog: Blog #10

Answer the following for a Blog Summary:

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

Drugs that ↑ DA activity/ restore dopaminergic activity with levodopa and dopamine agonists alleviate many of the motor features of the disorder.  Drugs that ↓ Cholinergic activity (to restore the normal balance of cholinergic and dopaminergic influences on the basal ganglia) with antimuscarinic drugs. By decreasing ACh activity = match the low DA activity = new balance achieved.

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

Amantadine has 3 three way MOA. It is a Metaffinoid potentiator of DA (↑ in DA activity - ↑ DA release ,↑ DA synthesis , blocks reuptake of DA), a NMDA antagonist (antidyskinetic effects) Adenosine A2a Antagonist (Adenosine Inhibits D2 receptors.\By blocking the adenosine receptor, improve D2 function & antiviral) This MOA enable amantadine to improve rigidity, tremors and bradykinesia which is often associated with parkinsonism. It is however only effective for a few weeks before disappearing.

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

MAO inhibitors – By inhibting MAO (the enzyme responsible for metabolising DA), the DA concentrations will increase.

COMT inhibitors - COMT metabolises L-dopa to 3OMD. Increased plasma levels of 3OMD leads to a weak therapeutic response with L-dopa (3OMD competes with L-dopa for active transport). Thus, a COMT-inhibitor extend the duration of action of L-dopa by: ↓ its peripheral metabolism , ↑ its bioavailability.

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

Ergot derivatives: Bromocriptine, Pramipexole

Non ergot derivatives: Ropinirole, Apomorphine

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

Pramipexole: Direct agonist at D3 receptors. 

Ropinirole: D2 agonist

Bromocriptine: D2 agonist

Pergolide: Directly stimulates both D1 and D2 receptors 

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

The MAO inhibitors are said to have neuroprotective effects such as Rasagiline. By preventing DA metabolism it ensures the DA neurons can be continuously be stimulated thus preventing the degeneration of DA neurons due to continuous stimulation.

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

By inhibiting MAO (the enzyme responsible for metabolising DA), the DA concentrations will increase. It ensures the DA neurons can be continuously be stimulated thus preventing the degeneration of DA neurons due to continuous stimulation.

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

COMT inhibitors - COMT metabolises L-dopa to 3OMD. Increased plasma levels of 3OMD leads to a weak therapeutic response with L-dopa (3OMD competes with L-dopa for active transport). Thus, a COMT-inhibitor extend the duration of action of L-dopa by: ↓ its peripheral metabolism , ↑ its bioavailability.

9. How does istradephyline act?

AdenosineA2A antagonist. Adenosine Inhibits D2 receptors.By blocking the adenosine receptor, improve D2 function & it is also an antiviral

10. Discuss the MOA of safinamide

MOA: Novel dual MOA. ↑ DA activity. Potent reversible inhibition of MAO-B .Inhibition of DA uptake ↓ Glutamate release