What are the two main groups of drugs used in the treatment of Parkinson's Disease (PD)

• Drugs that increase the dopamine activity
• Drugs that decrease cholinergic activity  

How does Amantadine act as a PD drug?

• Amantadine works by increasing the dopamine concentrations in the following ways
  • Increasing the release of dopamine
  • Increasing the synthesis of dopamine
  • Blocking the reuptake of dopamine

Discuss the mechanisms of antiparkinson's drugs that indirectly increase the concentration of dopamine.

• Carbidopa: This drug is an enzyme inhibitor. It inhibits the enzyme DOPA decarboxylase, which converts L-dopa into dopamine. By inhibiting the enzyme, the conversion of L-dopa peripherally is blocked. The L-dopa can then be transported into the brain and converted to dopamine, increasing dopamine concentrations. Benserazide is also a DOPA decarboxylase inhibitor 
• Entacapone: COMT inhibitor. By inhibiting this enzyme, less L-dopa will be converted to 3-O-methyldopa. This drug, therefore, decreases the peripheral metabolism of L-dopa. More L-dopa can be transported into the brain to be converted to dopamine, which will, in turn, increase the dopamine concentration in the brain

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

• Ergot derivatives
  • Bromocriptine

• Not-ergot derivatives
  • Pramipexole
  • Ropinirole

Dopamine receptors stimulated by each DA-agonist

• Bromocriptine: D2 receptors (partial agonist)
• Pramipexole: D3 receptors
• Ropinirole: D2 agonist

Which of the drugs above is neuroprotective? What does it mean?

• Neuroprotection refers to the ability of a drug to prevent neuronal cell death
• Bromocriptine, Pramipexole (is possibly neuroprotective)

What is the importance of MOA-B selective drugs in the treatment of PD?

• The selective MOA-B drugs are easier to use in patients with PD. Irreversible selective medicines are used for the treatment of akinesia and motor fluctuations.

How does a COMT inhibitor work in the treatment of PD?

• COMT is an enzyme responsible for the conversion of L-dopa into 3-O-methyldopa peripherally. L-Dopa and 3-O-methyldopa are transported through active transport processes and will compete to bind to active transporters. By inhibiting this COMT enzyme, L-dopa won't have to compete to attach to the transporters. More L-dopa will thus be transported across the BBB to be converted to dopamine. This will increase dopamine concentration.

How does Istradefylline act?

• It is a selective adenosine a2 antagonist used with carbidopa and levodopa for a patient's "off" episodes. This drug increases the dopamine activity

Discuss the mechanism of action of Safinamide.

• This drug works by reversibly inhibiting MAO-B and inhibiting the Dopamine reuptake. Therefore it increases dopamine activity.
• This drug also decreases the glutamate release, which reduces the formation of GABA and could decrease the excessive excitation caused when Ach binds to GABA