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

Drugs that increase dopamine and Anti-cholinergic drugs (decrease cholinergic activity).

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

It increases the activity of dopamine (Increases its release, synthesis and blocks its reuptake). It also is a NMDA antagonist (antidyskinetic effects) and is a adenosine A2a antagonist (block adenosine to improve D2 function).

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

MAOI – Inhibits MAO-B and -A, which increases dopamine as MAO breakdown dopamine.

COMT inhibitors – Inhibit COMT, which metabolises L-dopa to 3OMD peripherally and 3MT centrally. It therefore increases L-dopa, which is converted to dopamine.

Metaffinoid potentiator of Dopamine – increase dopamine release, increase dopamine synthesis, block dopamine reuptake.

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

Ergot derivatives: Bromocriptine, Pergolide

Non-ergot derivatives: Pramipexole, Ropinirole, Rotigotine

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

Pramipexole: D3 receptors

Ropinirole D2 receptors

Rotigotine: DA receptors

Bromocriptine: D2 receptors

Pergolide: D1 and D2 receptors

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

Pramipexole. It protects neurons.

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

It does not inhibit the breakdown of the other important MAO’s like adrenaline, noradrenaline and serotonin (which is broken down by MAO-A). It is selective for MAO-B, to inhibit the breakdown of Dopamine and Tyramine

• How do the COMT-inhibitors act in Parkinsonism?

It blocks COMT peripherally and some centrally. COMT metabolises L-Dopa to 3OMD (peripherally) and 3MT (centrally). COMT-inhibitors prevent this and in turn increase the dopamine concentrations.

• How does istradephyline act?

It is an Adenosine A2a antagonist – blocks adenosine (which inhibits D2 function), which in turn promotes D2 function.

• Discuss the MOA of safinamide

Safinamide is a novel dual MOAI. It increases dopamine activity, by potently inhibiting MOA-B (reversible) and inhibiting dopamine reuptake. It also decreases glutamate release.