K K Jain MD (Dr. Jain is a consultant in neurology and has no relevant financial relationships to disclose.)
Originally released December 22, 1998; last updated September 6, 2020; expires September 6, 2023

Historical note and terminology

Almost 1.5 centuries after the first description of Parkinson disease in 1817, dopamine was shown to be concentrated in the neostriatum of the brains of Parkinson disease patients (Bertler and Rosengren 1959). Dopaminergic deficits in patients with Parkinson disease were described a few years later (Barbeau et al 1962). It was also demonstrated that replenishment of dopamine through intravenous levodopa briefly improved the symptoms of patients with Parkinson disease (Birkmayer and Hornykiewicz 1961). The success of levodopa started the search for alternative ways to enhance dopaminergic transmission. One of the earlier dopamine agonists to be investigated was apomorphine. It had been used earlier, in 1951, for the treatment of Parkinson disease (Schwab et al 1951). Ergot derivatives then entered the dopamine agonist arena for the treatment of Parkinson disease. Bromocriptine is the best known example of this class of drugs.

Pramipexole, a non-ergot dopamine agonist, was synthesized in the United States and first manufactured in 1997 under the brand names of Mirapex and Mirapex ER (Wilson et al 2020). Initial clinical development of pramipexole was as a treatment for schizophrenia and depression, but this use appears to have been discontinued. The first biochemical and pharmacological studies on pramipexole were published in 1992 (Mierau and Schingnitz 1992). Pramipexole was first approved in the United States by the Food and Drug Administration in 1997. It was launched for the treatment of Parkinson disease as monotherapy and as an adjunct to levodopa. It has received approval from the European Medicines Evaluation Agency for the same indication. It was also approved for treatment of restless legs.

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