Blog #10 (SU 8.2)

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

Dopamine agonists and anticholinergic drugs.

 

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

Amantadine is a metaffinoid potentiator of dopamine. It works indirectly to increase dopamine activity, increase the release of dopamine, increase the synthesis of dopamine and blocks dopamine re-uptake thus making it effective as an anti-Parkinson’s drug. It is a NMDA antagonist thus having anti-dyskinetic effects. It is an adenosine-α_2A antagonist inhibiting D₂ receptors, by blocking the adenosine receptor you improve D₂ function. Amantadine improves rigidity, tremors and bradykinesia.

 

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

Drugs that indirectly increase dopamine concentration do not need to be converted to an active metabolite by enzymes, do not act directly on the post synaptic dopamine receptors and have no potentially toxic metabolites.

 

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

Ergot derivatives	Non-ergot derivatives
Bromocriptine	Pramipexole
	Ropinirole

 

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

• Bromocriptine: D₂ receptors
• Pramipexole: D₃ receptors
• Ropinirole: D₂ receptors

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

Rasagiline (MOA-B inhibitor) is classified as a neuron protecting drug because it increases the dopamine stores in the neurons of the brain.

 

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

MOA-B selective drugs are used in combination with levodopa to decrease the metabolism of dopamine thus prolonging the effect of levodopa.

 

• How do the COMT-inhibitors act in Parkinsonism?

COMT-inhibitors convert levodopa to 3OMD, this creates a weak response with levodopa because they compete for transport into the CNS. This increases the effect of levodopa.

 

• How does istradephyline act?

Istradephyline inhibits D₂ function. It does this by antagonising adenosine thus preventing inhibition of dopamine function. It is used as additional therapy to levodopa and carbidopa to decrease the on-off phenomenon.

 

• Discuss the MOA of safinamide

Safinamide has a novel dual mechanism of action. It 1. increases dopamine activity by potentiating reversible inhibition of MAO-B and inhibits dopamine re-uptake and 2. decreases glutamate release.

 

Reference list.

Brand, L. 2021. SU 8 Drugs Used In The Treatment Of Parkinsonism And Other Movement Disorders. https://efundi.nwu.ac.za/access/lessonbuilder/item/5911728/group/dd46f2da-d3be-402e-9ba7-2c5955cedd9d/English%20power%20point/English%20PP%202021/SU%208.pdf Date of access: 1 Apr. 2021. [PowerPoint presentation]

Katzung, B.G.  2018.  Basic & Clinical Pharmacology.  14^th ed.  California, San Francisco: McGraw-Hill Companies, Inc.