STEPTRACKERPHARMACOLOGY + NEUROLOGY | NEUROLOGY | HIGH-YIELD REVIEW

Parkinson, Alzheimer & MS Drugs

Parkinson drugs restore dopamine signaling (or cut excess ACh); Alzheimer drugs boost ACh or block glutamate; MS drugs modify the immune attack on myelin.

FOCUS ON
Parkinson: levodopa + carbidopa (peripheral DOPA decarboxylase inhibitor → less nausea, more brain levodopa); long-term "wearing off", on-off fluctuations, dyskinesias, hallucinations, orthostasis. Dopamine agonists (pramipexole, ropinirole; also restless legs): impulse-control disorders, sleep attacks. MAO-B inhibitors (selegiline, rasagiline, safinamide). COMT inhibitors (entacapone, tolcapone — hepatotoxic) prolong levodopa. Amantadine: ↑ dopamine release, NMDA block — dyskinesias; livedo reticularis. Benztropine, trihexyphenidyl: tremor in young patients. Avoid D2 blockers (haloperidol, metoclopramide). Alzheimer: AChE inhibitors (donepezil, rivastigmine, galantamine) — bradycardia, GI; memantine (NMDA antagonist) — moderate–severe; lecanemab, donanemab (anti-amyloid; ARIA edema/hemorrhage). MS: relapses → high-dose IV steroids, plasmapheresis; disease-modifying — interferon-β, glatiramer, natalizumab (PML), fingolimod (bradycardia, macular edema), ocrelizumab (anti-CD20), dimethyl fumarate, teriflunomide; dalfampridine (K⁺ block, walking). ALS: riluzole (↓ glutamate), edaravone. Huntington: tetrabenazine (VMAT2).
DRUG
MECHANISM
USE
ADVERSE · NOTES
Levodopa-carbidopa
Dopamine precursor crosses BBB; carbidopa blocks peripheral conversion
Parkinson (most effective)
Dyskinesia, on-off, hallucinations, orthostasis, arrhythmias; avoid with nonselective MAOI
Pramipexole · ropinirole · rotigotine
Direct D2/D3 agonists
Early Parkinson, restless legs
Impulse-control (gambling, hypersexuality), sleep attacks, edema, hallucinations
Bromocriptine · apomorphine
Ergot D2 agonist · rescue SC agonist
Prolactinoma · "off" episodes
Apomorphine: severe nausea (give antiemetic, not ondansetron)
Selegiline · rasagiline · safinamide
MAO-B inhibitors → ↓ dopamine breakdown
Early Parkinson, adjunct
Insomnia (selegiline → amphetamine metabolites), serotonin syndrome with SSRIs/meperidine
Entacapone · tolcapone · opicapone
COMT inhibitors → ↓ peripheral levodopa breakdown
Wearing-off
Tolcapone hepatotoxicity; orange urine (entacapone)
Amantadine
↑ Dopamine release, NMDA antagonist
Levodopa dyskinesias, early PD; influenza A (old)
Livedo reticularis, ankle edema, hallucinations
Benztropine · trihexyphenidyl
Central muscarinic antagonists
Tremor-predominant PD (young), drug-induced parkinsonism
Confusion, retention — avoid in elderly
Pimavanserin
5-HT2A inverse agonist (no D2 block)
Parkinson disease psychosis
QT; quetiapine/clozapine alternatives
Donepezil · rivastigmine · galantamine
AChE inhibitors
Alzheimer (all stages), Lewy body, PD dementia
Nausea, diarrhea, bradycardia, syncope, vivid dreams
Memantine
NMDA receptor antagonist (↓ excitotoxicity)
Moderate–severe Alzheimer
Dizziness, confusion, hallucinations
Lecanemab · donanemab
Anti-amyloid-β antibodies
Early Alzheimer with amyloid
ARIA (cerebral edema, microbleeds) — APOE4 risk
MS disease-modifying
Interferon-β, glatiramer · natalizumab (α4 integrin) · fingolimod (S1P) · ocrelizumab (CD20) · dimethyl fumarate
Relapsing MS (ocrelizumab also primary progressive)
Natalizumab PML (JC virus); fingolimod bradycardia, macular edema; interferon flu-like, depression
Riluzole · edaravone
↓ Glutamate release · free-radical scavenger
ALS (modest survival benefit)
Riluzole hepatotoxicity
Tetrabenazine · deutetrabenazine · valbenazine
VMAT2 inhibitors → deplete dopamine
Huntington chorea, tardive dyskinesia
Depression, suicidality, parkinsonism

Mechanism — boosting levodopa

Levodopa in gut and blood
→
Carbidopa blocks DDCCOMT inhibitors block 3-O-methylation
→
More crosses BBB
→
Converted to dopamine in striatumMAO-B inhibitors slow its breakdown

Parkinson treatment choice

PATIENT
PREFER
WHY
Older, disabling symptoms
Levodopa-carbidopa
Most effective
Younger, mild
MAO-B inhibitor or agonist
Delay dyskinesia
Tremor, young
Anticholinergic
Tremor relief
Psychosis
Pimavanserin, quetiapine
No D2 blockade

How it's tested

COMMON CONFUSIONCarbidopa doesn't cross the BBB — that's the point: it blocks conversion only outside the brain, lowering nausea and hypotension.
THE TRAPHaloperidol or metoclopramide in a Parkinson or Lewy body patient → severe rigidity and possible NMS; choose quetiapine or pimavanserin.
YOUR APPROACHDisease → neurotransmitter imbalance → drug that corrects it → effect of overshooting (dyskinesia, psychosis, cholinergic effects).

If you see… think…

New gambling habit after Parkinson drug → dopamine agonist
Purplish mottled skin on legs → amantadine (livedo reticularis)
Liver failure on Parkinson drug → tolcapone
Writhing movements at peak levodopa dose → dyskinesia
Bradycardia and syncope on dementia drug → AChE inhibitor
NMDA antagonist for Alzheimer → memantine
Progressive multifocal leukoencephalopathy in MS → natalizumab
First-dose bradycardia on MS pill → fingolimod
Chorea treatment depleting dopamine → tetrabenazine
Brain edema on MRI after anti-amyloid infusion → ARIA