Pramipexole, sold under the brand Mirapex among others, is medication used to treat Parkinson's disease (PD) and restless legs syndrome (RLS). In PD it may be used alone or together with levodopa. It is taken by mouth.
|Trade names||Mirapex, Mirapexin, Sifrol|
|Elimination half-life||8–12 hours|
|Excretion||Urine (90%), Feces (2%)|
|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||211.324 g/mol g·mol−1|
|3D model (JSmol)|
Common side effects include nausea, headache, feeling tired, trouble sleeping, dry mouth, and hallucinations. Serious side effects may include an urge to gamble or have sex, heart failure, and low blood pressure. Use in pregnancy and breastfeeding is of unclear safety. It is a dopamine agonist of the non-ergoline class.
Pramipexole was approved for medical use in the United States in 1997. It is available as a generic medication. A month supply in the United Kingdom costs the NHS about 8.40 £ as of 2019. In the United States the wholesale cost of this amount is about 5 USD. In 2016 it was the 204th most prescribed medication in the United States with more than 2 million prescriptions.
- Peripheral edema
- Hyperalgesia (body aches and pains)
- Nausea and vomiting
- Sedation and somnolence
- Decreased appetite and subsequent weight loss
- Orthostatic hypotension (resulting in dizziness, lightheadedness, and possibly fainting, especially when standing up)
- Hallucinations (seeing, hearing, smelling, tasting or feeling things that are not there), amnesia and confusion
- Twitching, twisting, or other unusual body movements
- Unusual tiredness or weakness
Several unusual adverse effects of pramipexole (and related D3-preferring dopamine agonist medications such as ropinirole) may include compulsive gambling, punding, hypersexuality, and overeating, even in patients without any prior history of these behaviours. Pramipexole may cause paradoxical worsening of restless legs syndrome in some cases. Use in pregnancy and breastfeeding is of unclear safety.
- D2S receptor (Ki = 3.9 nM; IA = 130%)
- D2L receptor (Ki = 2.2 nM; IA = 70%)
- D3 receptor (Ki = 0.5 nM; IA = 70%)
- D4 receptor (Ki = 5.1 nM; IA = 42%)
Pramipexole also possesses low/insignificant affinity (500–10,000 nM) for the 5-HT1A, 5-HT1B, 5-HT1D, and α2-adrenergic receptors. It has negligible affinity (>10,000 nM) for the D1, D5, 5-HT2, α1-adrenergic, β-adrenergic, H1, and mACh receptors. All sites assayed were done using human tissues.
While pramipexole is used clinically (see below), its D3-preferring receptor binding profile has made it a popular tool compound for preclinical research. For example, pramipexole has been used (in combination with D2- and or D3-preferring antagonists) to discover the role of D3 receptor function in rodent models and tasks for neuropsychiatric disorders. Of note, it appears that pramipexole, in addition to having effects on dopamine D3 receptors, may also affect mitochondrial function via a mechanism that remains less understood. A pharmacological approach to separate dopaminergic from non-dopaminergic (e.g. mitochondrial) effects of pramipexole has been to study the effects of the R-stereoisomer of pramipexole (which has much lower affinity to the dopamine receptors when compared to the S-isomer) side-by-side with the effects of the S-isomer.
Parkinson's disease is a neurodegenerative disease affecting the substantia nigra, a component of the basal ganglia. The substantia nigra has a high quantity of dopaminergic neurons, which are nerve cells that release the neurotransmitter known as dopamine. When dopamine is released, it may activate dopamine receptors in the striatum, which is another component of the basal ganglia. When neurons of the substantia nigra deteriorate in Parkinson's disease, the striatum no longer properly receives dopamine signals. As a result, the basal ganglia can no longer regulate body movement effectively and motor function becomes impaired. By acting as an agonist for the D2, D3, and D4 dopamine receptors, pramipexole may directly stimulate the underfunctioning dopamine receptors in the striatum, thereby restoring the dopamine signals needed for proper functioning of the basal ganglia.
Pramipexole has been evaluated for the treatment of sexual dysfunction experienced by some users of selective serotonin reuptake inhibitor (SSRI) antidepressants. Pramipexole has shown effects on pilot studies in a placebo-controlled proof of concept study in bipolar disorder. It is also being investigated for the treatment of clinical depression and fibromyalgia.
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