Basal Ganglia Pharmacology

Question 1

Levodopa

Answer 1

Precursor to dopamine. Restores dopaminergic activity in striatum. Activation of D1 and D2 receptors.
*Decreases akinesia, rigidity, and tremor. Only effective early in therapy due to progressive loss of dopaminergic neurons.

Question 2

Levodopa + Carbidopa

Sinemet

Answer 2

Carbidopa inhibits conversion of l-dopa to dopamine in periphery by blocking AAAD, but since it does not cross BBB, it doesn’t block AAAD in brain! Decrease L-DOPA dose by 75%.

Question 3

Trihexyphenidyl

Answer 3

Muscarinic antagonist (anticholinergics)

Question 4

Amantadine

Answer 4

• Antiviral drug
• Mechanism unclear: NMDA receptor antagonist
• Less effective than levodopa
• Short lived benefits

Question 5

Pramipexole

Answer 5

Agonist at D2 class receptors (D2 and D3)

Question 6

Selegiline

Answer 6

Monoamine oxidase-B inhibitor (metabolizes dopamine).

Question 7

Entacapone

Answer 7

• Combined with L-DOPA or L-DOPA and carbidopa

- Decreases peripheral metabolism of L-DOPA by COMT (catechol-O-methyltransferase)

Question 8

What are the main side effects of L-DOPA?

Answer 8

• Dyskinesias: abnormal involuntary movements
• On-Off phenomenon: sudden and rapid loss of clinical effect
• Wearing off phenomenon: drug effect wears off between doses, symptoms fluctuate
• Confusion, anxiety, agitation, insomnia, nightmares, depression
• Psychotic reactions-schizophrenia-like delusions and hallucinations
• Effects related to peripheral dopamine (orthostatic hypotension, nausea, vomiting, anorexia)