Pramipexole

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Pramipexole
File:Pramipexole.svg
File:Pramipexole ball-and-stick model.png
Systematic (IUPAC) name
(S)-N  6-propyl-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine
Clinical data
Trade names Mirapex, Mirapexin, Sifrol
AHFS/Drugs.com monograph
MedlinePlus a697029
Pregnancy
category
  • AU: B3
  • US: C (Risk not ruled out)
Legal status
  • ℞ (Prescription only)
Routes of
administration		 Oral
Pharmacokinetic data
Bioavailability >90%
Protein binding 15%
Biological half-life 8–12 hours
Excretion Urine (90%), Feces (2%)
Identifiers
CAS Number 104632-26-0 YesY
ATC code N04BC05 (WHO)
PubChem CID: 119570
IUPHAR/BPS 953
DrugBank DB00413 YesY
ChemSpider 106770 YesY
UNII 83619PEU5T YesY
KEGG D05575 YesY
ChEBI CHEBI:8356 YesY
ChEMBL CHEMBL301265 YesY
Chemical data
Formula C10H17N3S
Molecular mass 211.324 g/mol
  • n1c2c(sc1N)C[C@@H](NCCC)CC2
  • InChI=1S/C10H17N3S/c1-2-5-12-7-3-4-8-9(6-7)14-10(11)13-8/h7,12H,2-6H2,1H3,(H2,11,13)/t7-/m0/s1 YesY
  • Key:FASDKYOPVNHBLU-ZETCQYMHSA-N YesY
  (verify)

Pramipexole (Mirapex, Mirapexin, Sifrol) is a dopamine agonist of the non-ergoline class indicated for treating Parkinson's disease (PD)[1] and restless legs syndrome (RLS).[2]

Pharmacology

Pramipexole acts as a partial/full agonist at the following receptors:[3][4]

Pramipexole also possesses low/insignificant affinity (500–10,000 nM) for the 5-HT1A, 5-HT1B, 5-HT1D, and α2-adrenergic receptors.[3][5] It has negligible affinity (>10,000 nM) for the D1, D5, 5-HT2, α1-adrenergic, β-adrenergic, H1, and mACh receptors.[3][5] All sites assayed were done using human tissues.[3][4]

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 interrogate the role of D3 receptor function in rodent models and tasks for neuropsychiatric disorders.[6] 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.[7]

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.

Bipolar depression

In a single controlled study of twenty one patients, pramipexole was found to be highly effective in the treatment of bipolar depression. Treatment was initiated at 0.125 mg three times a day and increased at a rate of 0.125 mg three times a day to a limit of 4.5 mg daily until the patients' condition satisfactorily responded to the medication or they could not abide the side effects. The final average dosage was 1.7 ± 0.9 mg daily. The incidence of hypomania in the treatment group was no greater than in the control group, although the size of the study is too small to determine risks for manic switch.[8]

Unipolar depression

In one controlled study, pramipexole was shown to be efficacious in the treatment of unipolar depression.[9]cited in[8]

Side effects

Common side effects of pramipexole may include:[10][11]

Several unusual adverse effects of pramipexole (and related D3-preferring dopamine agonist medications such as ropinirole) may include compulsive gambling, punding, hypersexuality, and overeating,[12] even in patients without any prior history of these behaviours.[13]

Research

Pramipexole has been evaluated for the treatment of cluster headache[citation needed] and to counteract problems with sexual dysfunction experienced by some users of selective serotonin reuptake inhibitor (SSRI) antidepressants.[14] Pramipexole has shown effects on pilot studies in a placebo-controlled proof of concept study in bipolar disorder.[8][15][16] It is also being investigated for the treatment of clinical depression and fibromyalgia.[17][18][19]

See also

References

  1. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  2. ↑ National Prescribing Service (2009). "Pramipexole for Parkinson's Disease". Medicines Update. Available at http://www.nps.org.au/consumers/publications/medicine_update/issues/Pramipexole_for_Parkinsons_disease
  3. ↑ 3.0 3.1 3.2 3.3 Lua error in package.lua at line 80: module 'strict' not found.
  4. ↑ 4.0 4.1 Lua error in package.lua at line 80: module 'strict' not found.
  5. ↑ 5.0 5.1 Lua error in package.lua at line 80: module 'strict' not found.
  6. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  7. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  8. ↑ 8.0 8.1 8.2 Lua error in package.lua at line 80: module 'strict' not found.
  9. ↑ Corrigan MH, Denahan AQ, Wright CE, Ragual RJ, Evans DL (2000): Comparison of pramipexole, fluoxetine, and placebo in patients with major depression. Depress Anxiety 11:58 –65.
  10. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  11. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  12. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  13. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  14. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  15. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  16. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  17. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  18. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  19. ↑ Lua error in package.lua at line 80: module 'strict' not found.

External links

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