Classics in Chemical Neuroscience: Pramipexole

Pramipexole was first manufactured by Pharmacia and Upjohn in July 1997 under the United States brand names of Mirapex and Mirapex ER. Pramipexole is classified as a nonergoline aminobenzothiazole compound that selectively agonizes the dopamine D₂-like receptor subfamily, which includes the D₂, D₃, and D₄ receptor subtypes. Pramipexole is a unique compound in its therapeutic potential because it has D₃-preferring properties. The D₃ receptor target has implications in both motor and psychiatric symptoms of Parkinson's disease, restless leg syndrome, and bipolar and unipolar depression. Currently, pramipexole is approved to treat signs and symptoms of idiopathic Parkinson's disease and moderate to severe symptoms of primary restless leg syndrome. Parkinson's disease is characterized by tremor, bradykinesia, rigidity, gait disorders, and a disturbance of posture due to a decrease in dopamine stores in the substantia nigra with the consequent presence of Lewy bodies. Restless leg syndrome is a neurologic sensorimotor disorder characterized by a compelling urge to move the body/limb to relieve this uncomfortable sensation. In this Review, we will discuss the synthesis, drug metabolism, pharmacology, adverse effects, history, and the importance of pramipexole to neuroscience and describe its role in therapy.