Pramipexole

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Pramipexole
Pramipexole.svg
Pramipexole ball-and-stick model.png
Clinical data
Pronunciation/ˌpræmɪˈpɛksoʊl/
Trade namesMirapex, Mirapexin, Sifrol, others
AHFS/Drugs.comMonograph
MedlinePlusa697029
License data
Pregnancy
category
Routes of
administration		By mouth
ATC code
Legal status
Legal status
  • US: ℞-only [2][3]
  • EU: Rx-only [4][5]
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability>90%
Protein binding15%
Elimination half-life8–12 hours
ExcretionUrine (90%), Feces (2%)
Identifiers
IUPAC name
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.124.761 Edit this at Wikidata
Chemical and physical data
FormulaC10H17N3S
Molar mass211.33 g·mol−1
3D model (JSmol)
SMILES
InChI
  

Pramipexole, sold under the brand Mirapex among others, is medication used to treat Parkinson's disease (PD) and restless legs syndrome (RLS).[6] In Parkinson's disease it may be used alone or together with levodopa.[6] It is taken by mouth.[6] Pramipexole is a dopamine agonist of the non-ergoline class.[6]

Pramipexole was approved for medical use in the United States in 1997.[6] Use in pregnancy and breastfeeding is of unclear safety.[1] It is available as a generic medication.[7] In 2018, it was the 196th most commonly prescribed medication in the United States, with more than 2 million prescriptions.[8][9]

Medical uses[]

Pramipexole is used in the treatment of Parkinson's disease (PD) and restless legs syndrome (RLS).[6] Use in pregnancy and breastfeeding is of unclear safety.[1]

Side effects[]

Common side effects of pramipexole may include:[10][2][3]

  • Headache
  • Peripheral edema[11]
  • 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)
  • Insomnia
  • 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
  • Impulsive-compulsive behaviors: Pramipexole (and related D3-preferring dopamine agonist medications such as ropinirole) can induce "impulsive-compulsive spectrum disorders"[12] such as compulsive gambling, punding, hypersexuality, and overeating, even in people without any prior history of these behaviours.[13][14][15]
  • Augmentation:[a] Especially when used to treat restless legs syndrome, long-term pramipexole treatment may exhibit drug augmentation, which is "an iatrogenic worsening of RLS symptoms following treatment with dopaminergic agents"[16] and may include an earlier onset of symptoms during the day or a generalized increase in symptoms.[17][18][19]

Pharmacology[]

The activity profile of pramipexole at various sites has been characterized as follows:

Activities of pramipexole at various sites[20][21]
Site Affinity (Ki, nM) Efficacy (Emax, %) Action
D2S 3.9 130 Full agonist
D2L 2.2 70 Partial agonist
D3 0.5 70 Partial agonist
D4 5.1 42 Partial agonist
Notes: Pramipexole also possesses lower affinity (500–10,000 nM) for the 5-HT1A, 5-HT1B, 5-HT1D, and α2-adrenergic receptors.[20][22] It has negligible affinity (>10,000 nM) for the D1, D5, 5-HT2, α1-adrenergic, β-adrenergic, H1, and mACh receptors.[20][22] All sites were assayed using human materials.[20][21]

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.[23] 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.[24]

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.

Society and culture[]

Brand names[]

Brand names include Mirapex, Mirapex ER, Mirapexin, Sifrol, Glepark, and Oprymea.[citation needed]

Research[]

Pramipexole has been evaluated for the treatment of sexual dysfunction experienced by some users of selective serotonin reuptake inhibitor (SSRI) antidepressants.[25] Pramipexole has shown effects on pilot studies in a placebo-controlled proof of concept study in bipolar disorder.[26][27][28] It is also being investigated for the treatment of clinical depression and fibromyalgia.[29][30][31]

Notes[]

  1. ^ The term "augmentation" has different meanings depending on the context. In the context of the pharmacological management of psychiatric disorders, for example, it means enhancing treatment effects by adding a second drug (or other treatment intervention). In the present context, augmentation has the meaning given above (in the body of the article).

References[]

  1. ^ Jump up to: a b c "Pramipexole Pregnancy and Breastfeeding Warnings". Drugs.com. Retrieved 3 March 2019.
  2. ^ Jump up to: a b "Mirapex- pramipexole dihydrochloride tablet". DailyMed. 1 March 2020. Retrieved 17 October 2020.
  3. ^ Jump up to: a b "Mirapex ER- pramipexole dihydrochloride tablet, extended release". DailyMed. 5 February 2020. Retrieved 17 October 2020.
  4. ^ "Sifrol EPAR". European Medicines Agency. Retrieved 17 October 2020.
  5. ^ "Mirapexin EPAR". European Medicines Agency. Retrieved 17 October 2020.
  6. ^ Jump up to: a b c d e f "Pramipexole Dihydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 22 March 2019.
  7. ^ British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. pp. 417–418. ISBN 9780857113382.
  8. ^ "The Top 300 of 2021". ClinCalc. Retrieved 18 February 2021.
  9. ^ "Pramipexole Dihydrochloride - Drug Usage Statistics". ClinCalc. Retrieved 18 February 2021.
  10. ^ "MedlinePlus Drug Information: Pramipexole (Systemic)". United States National Library of Medicine. Archived from the original on 26 September 2006. Retrieved 27 September 2006.
  11. ^ Tan EK, Ondo W (2000). "Clinical characteristics of pramipexole-induced peripheral edema". Arch Neurol. 57 (5): 729–732. doi:10.1001/archneur.57.5.729. PMID 10815140.
  12. ^ Napier, T. Celeste; Kirby, Alana; Persons, Amanda L. (2020). "The role of dopamine pharmacotherapy and addiction-like behaviors in Parkinson's disease". Progress in Neuro-psychopharmacology and Biological Psychiatry. 102: 109942. doi:10.1016/j.pnpbp.2020.109942. PMID 32272129. S2CID 215237629. ... features of ICSDs [impulsive-compulsive spectrum disorders] during D2/D3R treatment are consistent with the pharmacological profile of the drugs, the known role of D2/D3R in these behaviors, and the neuroanatomical substrates of D2/D3R-expressing brain systems of ICSDs as shown by modern human imaging studies. While we pose that D2/D3R agonist treatment is sufficient to mediate ICSDs, there likely are many factors that overlay this profile, e.g., genetic vulnerabilities, brain disease state, and maladaptations to the chronic therapy.
  13. ^ Bostwick JM, Hecksel KA, Stevens SR, Bower JH, Ahlskog JE (April 2009). "Frequency of new-onset pathologic compulsive gambling or hypersexuality after drug treatment of idiopathic Parkinson disease". Mayo Clin. Proc. 84 (4): 310–6. doi:10.4065/84.4.310. PMC 2665974. PMID 19339647.
  14. ^ Moore TJ; Glenmullen J; Mattison DR (December 2014). "Reports of Pathological Gambling, Hypersexuality, and Compulsive Shopping Associated With Dopamine Receptor Agonist Drugs". JAMA Internal Medicine. 174 (12): 1930–1933. doi:10.1001/jamainternmed.2014.5262. PMID 25329919.
  15. ^ Wolters ECh; van der Werf YD; van den Heuvel OA (2008). "Parkinson's disease-related disorders in the impulsive-compulsive spectrum". J. Neurol. 255 Suppl 5: 48–56. doi:10.1007/s00415-008-5010-5. PMID 18787882. S2CID 24531331.
  16. ^ Winkelmann, Juliane; Allen, Richard P.; Högl, Birgit; Inoue, Yuichi; Oertel, Wolfgang; Salminen, Aaro V.; Winkelman, John W.; Trenkwalder, Claudia; Sampaio, Cristina (2018). "Treatment of restless legs syndrome: Evidence-based review and implications for clinical practice (Revised 2017)§". Movement Disorders. 33 (7): 1077–1091. doi:10.1002/mds.27260. ISSN 1531-8257. PMID 29756335. S2CID 21669996. … the specific goals of the current review were to … separately identify the RLS-specific side effect, which is augmentation.
  17. ^ "Pramipexole Monograph for Professionals". Drugs.com. Retrieved 11 December 2020. Augmentation of symptoms of restless legs syndrome (e.g., earlier onset of symptoms in the evening or afternoon, increase in symptoms, spread of symptoms to involve other extremities) reported; incidence increased with increasing duration of pramipexole treatment.
  18. ^ Winkelman, John W.; Armstrong, Melissa J.; Allen, Richard P.; Chaudhuri, K. Ray; Ondo, William; Trenkwalder, Claudia; Zee, Phyllis C.; Gronseth, Gary S.; Gloss, David; Zesiewicz, Theresa (2016). "Practice guideline summary: Treatment of restless legs syndrome in adults". Neurology. 87 (24): 2585–2593. doi:10.1212/WNL.0000000000003388. ISSN 0028-3878. PMC 5206998. PMID 27856776.
  19. ^ Salminen, Aaro V.; Winkelmann, Juliane (2018). "Restless Legs Syndrome and Other Movement Disorders of Sleep-Treatment Update". Current Treatment Options in Neurology. 20 (12): 55. doi:10.1007/s11940-018-0540-3. ISSN 1092-8480. PMID 30411165. S2CID 53242049. … augmentation of the RLS symptoms is a major limitation of oral dopaminergic therapy.
  20. ^ Jump up to: a b c d Kvernmo T, Härtter S, Burger E (August 2006). "A review of the receptor-binding and pharmacokinetic properties of dopamine agonists". Clinical Therapeutics. 28 (8): 1065–78. doi:10.1016/j.clinthera.2006.08.004. PMID 16982285.
  21. ^ Jump up to: a b Newman-Tancredi A, Cussac D, Audinot V, et al. (November 2002). "Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. II. Agonist and antagonist properties at subtypes of dopamine D(2)-like receptor and alpha(1)/alpha(2)-adrenoceptor". The Journal of Pharmacology and Experimental Therapeutics. 303 (2): 805–14. doi:10.1124/jpet.102.039875. PMID 12388667. S2CID 35238120.
  22. ^ Jump up to: a b Millan MJ, Maiofiss L, Cussac D, Audinot V, Boutin JA, Newman-Tancredi A (November 2002). "Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes". The Journal of Pharmacology and Experimental Therapeutics. 303 (2): 791–804. doi:10.1124/jpet.102.039867. PMID 12388666. S2CID 6200455.
  23. ^ Weber, M; Chang W; Breier M; Ko D; Swerdlow NR (December 2008). "Heritable strain differences in sensitivity to the startle gating-disruptive effects of D2 but not D3 receptor stimulation". Behav Pharmacol. 19 (8): 786–795. doi:10.1097/FBP.0b013e32831c3b2b. PMC 3255557. PMID 19020413.
  24. ^ Chang, W; Weber M; Breier MR; Saint Marie RL; Hines SR; Swerdlow NR (February 2012). "Stereochemical and neuroanatomical selectivity of pramipexole effects on sensorimotor gating in rats". Brain Res. 1437: 69–76. doi:10.1016/j.brainres.2011.12.007. PMC 3268831. PMID 22227455.
  25. ^ DeBattista C, Solvason HB, Breen JA, Schatzberg AF (2000). "Pramipexole augmentation of a selective serotonin reuptake inhibitor in the treatment of depression". J Clin Psychopharmacol. 20 (2): 274–275. doi:10.1097/00004714-200004000-00029. PMID 10770475.
  26. ^ Zarate CA, Payne JL, Singh J, et al. (July 2004). "Pramipexole for bipolar II depression: a placebo-controlled proof of concept study". Biol. Psychiatry. 56 (1): 54–60. doi:10.1016/j.biopsych.2004.03.013. PMID 15219473. S2CID 19613411.
  27. ^ Goldberg JF, Burdick KE, Endick CJ (March 2004). "Preliminary, randomized, double-blind, placebo-controlled trial of pramipexole added to mood stabilizers for treatment resistant bipolar depression". American Journal of Psychiatry. 161 (3): 161:564–566. doi:10.1176/appi.ajp.161.3.564. PMID 14992985.
  28. ^ Guy M. Goodwina; A. Martinez-Aranb; David C. Glahn c; Eduard Vieta b (November 2008). "Cognitive impairment in bipolar disorder: Neurodevelopment or neurodegeneration? An ECNP expert meeting report". European Neuropsychopharmacology. 18 (11): 787–793. doi:10.1016/j.euroneuro.2008.07.005. PMID 18725178. S2CID 18520604.
  29. ^ Lattanzi L, Dell'Osso L, Cassano P, Pini S, Rucci P, Houck PR, Gemignani A, Battistini G, Bassi A, Abelli M, Cassano GB (2002). "Pramipexole in treatment-resistant depression: a 16-week naturalistic study". Bipolar Disord. 4 (5): 307–314. doi:10.1034/j.1399-5618.2002.01171.x. PMID 12479663.
  30. ^ Cassano P, Lattanzi L, Soldani F, Navari S, Battistini G, Gemignani A, Cassano GB (2004). "Pramipexole in treatment-resistant depression: an extended follow-up". Depression and Anxiety. 20 (3): 131–138. doi:10.1002/da.20038. PMID 15549689. S2CID 23007562.
  31. ^ Holman AJ, Myers RR (2005). "A randomized, double-blind, placebo-controlled trial of pramipexole, a dopamine agonist, in patients with fibromyalgia receiving concomitant medications". Arthritis Rheum. 52 (8): 2495–2505. doi:10.1002/art.21191. PMID 16052595.

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