Parkinson's

Question 1

MOAb Inhibitors

Answer 1

• Rasagiline
• Selegiline

MOA:
Stop dopamine from being degraded in the pre-synaptic neurons (Conversion from dopamine to DOPAC) + protect residual dopamine vs oxidation

Question 2

COMT Inhibitors

Answer 2

• Entacapone
• Tolcapone

MOA:
Stop dopamine degradation from DOPAC to Homovanillic acid.
(!) May alleviate dystonias and motor fluctuations in long-term management of L-DOPA.
Optimises effect of L-DOPA when used in combination

Question 3

Increasing dopamine release

Answer 3

• Amantadine

MOA:
Inhibition of amine uptake, inhibition of MOA activity, release of dopamine (and noradrenaline) from monoaminergic terminals.

Question 4

Increasing dopamine synthesis

Answer 4

• L-DOPA/Levodopa
MOA: Dopaminergic nerve fibres take up L-DOPA. Converted by the enzyme DOPA decarboxylase to dopamine.

• Madopar (has PDCI Benserazide)
MOA: Contains peripheral decarboxylase inhibitor (PDCI) along with L-DOPA to prevent the conversion to dopamine to occur outside the BBB (causes nausea/vomiting due to stimulation of the chemoreceptor trigger zone).
Other PDCIs include carbidopa

Side effects:
• Nausea/vomiting
• Postural hypotension
• Psychosis
• Impulse-control disorders
• Excessive day-time sleepiness

Motor complications:
“On-off” effect
“Wearing-off” (“end-of-dose” deterioration)
Dyskinesia, dystonia

Question 5

Post synaptic dopamine receptor agonists

Answer 5

• Rotigotine (!) (ropinirole, pramipexole) - non-selective, has recently been introduced. It can be given as a transdermal patch (continuous administration over 24hrs)
• Apomorphine - Non-selective potent emetic: that can be given as infusion.
• Bromocriptine - Much higher affinity for D1 than D2, also used for other types of infertility.
• Pergolide, Quinpirole - Show little selectivity between D1 and D2 families of receptors.

Question 6

Anticholinergics

Answer 6

• Orphenadrine, procyclidine, trihexyphenidyl

MOA: Dopamine loss leads to hyperactivity of cholinergic cells.
They increase dopamine release, inhibit dopamine re-uptake, inhibit overactivity.
Side Effects: dry mouth, flushed (hot) skin, dilation of pupils, tachycardia etc…