CNS Drugs

• Dopamine Agonists
  • General
    • Psychosis more likely with Dopamine agonists
    • Indicated for RLS/Parkinsons
    • Less likely to produce on-off effect
  • Non-Ergot Alkaloids
    • Pramipexole (Mirapex)
      • MOA: D3 receptor agonist
    • Ropinirole
      • MOA: D2 receptor agonist
      • SE: May exacerbate impulse control disorders
  • Ergot Alkaloid
    • Bromocriptine
      • MOA: Dopamine receptor agonist
• Amantadine
  • MOA: Increased endogenous dopamine release, Inhibits reuptake
• Carbidopa-Levodopa (Sinemet)
  • MOA:
    • Carbidopa: Peripheral DOPA decarboxylase inhibitor
    • Levodopa: Dopamine precursor
  • Acute SE:
    • Increased Peripheral Dopamine: GI distress, Arrythmia, Orthostatic hypotension
    • Increased Central Dopamine: Neuropsych symptoms
  • Chronic SE:
    • Response Fluctuations (wearing-off effect)
      • Not related to dose
    • Dyskinesias (Choreoathetosis) of face and extremities
  • CI: Psychosis
• COMT Inhibitors
  • Tolcapone (Tasmar)
    • CNS active (can cross BBB)
    • Associated with Liver failure
  • Entacapone (Comtan)
    • Not active in CNS
• Acetylcholinesterase Inhibitors
  • Galantamine
    • 4mg BID for 4 weeks and re-eval, max is 16mg BID
    • Least expensive, minimal SD
• Pimavanserin (Nuplazid)
  • Dose: 34mg once daily only
  • MOA: Non-dopaminergic atypical antipsychotic via antagonism and inverse agonism at 5HT2A receptors, minimal 5HT2C, no 5HT2B or D2
    • Metabolized CYP3A4 and CYP 3A5
  • Use: Psychosis due to Parkinson Disease, drug induced or regular
    • Reduces hallucinations without worsening parkinsonism
  • SE: Nausea (7%), Constipation (4%), Peripheral Edema (7%), Confusion (6%), possible QTc prolongation