Therapeutic and Diagnostic Agents for Parkinson's Disease

Abstract

This article summarizes the neurobiology of Parkinson's disease and medicinal chemistry relevant to treatment of this neurodegenerative disorder with neuropsychiatric complications. The article also surveys basic clinical features of Parkinson's disease, its neuropathophysiology and etiology. Considered are genetic, maturational, metabolic, and environmental contributors to risk for the disease. Pharmacotherapy for Parkinson's disease includes l ‐dopa to counter cerebral dopamine deficiency, direct dopaminergic agonists, and agents that prolong the actions of l ‐dopa or dopamine by preventing their metabolism by peripheral aromatic amino acid decarboxylase, catechol‐ O ‐methyltransferase, or monoamine oxidase. Additional drugs acting on nondopaminergic systems include muscarinic acetylcholine, adenosine, and l ‐glutamate antagonists, as well as serotonin (5‐hydroxytryptamine) agonists. Agents used to diagnose Parkinson's disease and monitor its progression include radioactive compounds used to image brain l ‐dopa and dopamine neurotransporters and dopamine receptors. Finally, potential contributions are considered of medicinal chemistry to improve pharmacotherapy of Parkinson's disease.