Clinical meaning
Parkinson disease results from progressive loss of dopaminergic neurons in the substantia nigra pars compacta, creating a dopamine-acetylcholine imbalance in the striatum. Pharmacotherapy targets multiple points in the dopaminergic pathway: levodopa (dopamine precursor) crosses the blood-brain barrier and is converted to dopamine by aromatic L-amino acid decarboxylase (AADC); carbidopa inhibits peripheral AADC to prevent peripheral conversion and reduce nausea/hypotension; COMT inhibitors (entacapone, opicapone) block peripheral degradation of levodopa extending its half-life; MAO-B inhibitors (selegiline, rasagiline, safinamide) prevent synaptic dopamine breakdown; dopamine agonists (pramipexole, ropinirole, rotigotine) directly stimulate D2/D3 receptors; and anticholinergics (benztropine, trihexyphenidyl) restore balance by reducing cholinergic excess.
Diagnosis & workup
Diagnostics & workup: - Clinical diagnosis based on bradykinesia plus resting tremor or rigidity (MDS criteria) - Levodopa challenge test (>30% improvement in UPDRS motor score confirms dopamine-responsive parkinsonism) - DaTscan (ioflupane I-123 SPECT) to differentiate PD from essential tremor or drug-induced parkinsonism - MRI brain to exclude structural causes (normal in PD) - Genetic testing (LRRK2, GBA) in young-onset or familial cases - Autonomic function testing for multisystem atrophy differentiation - UPDRS (Unified Parkinson Disease Rating Scale) for severity staging and treatment monitoring