Pharmacology  ·  Antiparkinson Drugs

Amantadine and Anticholinergic Agents

Dual-mechanism dopaminergic-glutamatergic drug and the oldest class in Parkinson's disease therapy

• Amantadine has a dual mechanism — it enhances presynaptic dopamine release and blocks NMDA receptors, making it the only drug with established efficacy specifically for levodopa-induced dyskinesias; it is also used as mild monotherapy in early disease.
• Amantadine's distinctive adverse effects include livedo reticularis (mottled purplish skin discoloration, benign) and peripheral edema; confusion and hallucinations are dose-dependent and more prominent in the elderly; renal excretion requires dose reduction in renal impairment.
• Anticholinergic agents (benztropine, trihexyphenidyl) reduce striatal cholinergic excess — the neurotransmitter imbalance that drives tremor and rigidity — making them the preferred class specifically for tremor-predominant Parkinson's disease.
• Anticholinergics improve tremor and rigidity but have minimal effect on bradykinesia, the most disabling feature; benztropine also has an acute injectable use for drug-induced dystonia.
• Anticholinergic drugs are on the Beers Criteria as potentially inappropriate for patients over 65 — central muscarinic blockade impairs memory and can precipitate delirium; levodopa-carbidopa is the preferred agent in elderly patients.