Blog 10

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

Drugs that increase Dopamine activity in the brain like, L-dopa or dopamine agonists or drugs that decrease the cholinergic activity in the brain like anticholinergic drugs.

In what way does amantadine act as a antiparkinsonism drug?

Amantadine indirectly treats Parkinson’s, because Amantadine is an metaffinoid potentiator on the dopamine receptor it potentiates the release and synthesis of dopamine and it also blocks the re-uptake of dopamine and thus its metabolism. This will increase dopamine’s effect on the body and restore balance between the Ach and dopamine in the brain and thus decrease the symptoms of Parkinson’s.

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

Drugs like Amantadine and MAO-B inhibitors indirectly increases dopamine concentrations because, as explained above Amantadine is a metaffiniod potentiator thus it binds to a dopamine receptor and potentiates its effect in this case it will increase dopamine release and synthesis, it also blockes the reuptake of dopamine.

MAO-b inhibitors indirectly increases dopamine concentration by blocking the metabolism of dopamine.

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

Ergot derivatives	Non ergot derivatives
Bromocriptine (Older drug less used)	Pramipexole (Newer drugs)
	Ropinirole

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

• Dopamine 2 receptors agonists: Bromocriptine and Ropinirole
• Dopamine 3 receptors agonist: Pramipexole

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

Pramipexole, it is a neuroprotective which means it is drug that can alter the course of a ischemic event in an neuron, in other words it alters the metabolic event of the neurons to decrease the damage that is done to the neuron. In the case of a Parkinson’ disease cycle in which the dopamine neurons die over time the neuroprotective drugs can stop or slow this degradation down.

 

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

These drugs is isomers of dopamine which means is can bind to MAO-B receptors and block them from dopamine this will increase the amount of dopamine centrally and this will help to get the balance between dopamine and Ach more normal because this balance is inadequate in Parkinson patients.

How do the COMT-inhibitors act in Parkinsonism?

COMT inhibiter drugs block COMT enzymes, this enzyme metabolizes L-Dopa to 3-O-methyl dopa, and by blocking this enzyme the amount and life time of the L-Dopa Centrally will increase and the L-Dopa can be converted to dopamine by carboxylase, which will help to improve the symptoms of Parkinson disease.

How does istradephyline act?

Istradephyline binds to Adenosine A_2A and blocks its effects. It is added to L-dopa and carbidopa combinations to improve a patient’s off episodes, patient struggles to move voluntarily.

Discuss the MOA of safinamide

Safinamide has a dual action it increases dopamine activity by blocking MAO-B enzymes that metabolises L-Dopa, this increases dopamine concentration and it inhibits dopamine reuptake, it also decrease glutamate release.

Both these actions is beneficial for the treatment of Parkinsons disease.