Dopamine agonist

Dopamine receptor agonist
Drug class
Class identifiers
Use Parkinson's disease, Attention deficit/hyperactivity disorder(ADHD), restless legs syndrome, clinical depression, etc.
ATC code N04
Biological target Dopamine receptors
External links
MeSH D010300
In Wikidata

A dopamine receptor agonist is a compound that activates dopamine receptors. Dopamine receptor agonists activate signaling pathways through trimeric G-proteins and β-arrestins, ultimately leading to changes in gene transcription.

Today, for several dopamine receptor subtypes (D1, D2, D3) agonists are known, that differentially address these signalling pathways. They are called biased agonists.[1][2][3][4][5]

Uses

Dopamine

Some medical drugs act as dopamine agonists and can treat hypodopaminergic (low dopamine) conditions; they are typically used for treating Parkinson's disease, attention deficit/hyperactivity disorder (in the form of stimulants) and certain pituitary tumors (prolactinoma), and may be useful for restless legs syndrome (RLS). Both ropinirole and pramipexole are FDA-approved for the treatment of RLS. There is also an ongoing clinical trial to test the effectiveness of the dopamine agonist ropinirole in reversing the symptoms of SSRI-induced sexual dysfunction.[6] Additionally, a systematic review and meta-analysis concluded that prophylactic treatment with cabergoline reduces the incidence, but not the severity, of ovarian hyperstimulation syndrome (OHSS), without compromising pregnancy outcomes, in females undergoing stimulated cycles of in vitro fertilization (IVF).[7]

Side-effects

Some of the common side effects of dopamine agonists include:[8][9]

Examples

Examples of dopamine agonists include:

Partial agonist

Agonists of full/unknown efficacy

Some, such as fenoldopam, are selective for dopamine receptor D1.[15]

Indirect agonists

There are two classes of drugs that act as indirect agonists of dopamine receptors: dopamine reuptake inhibitors and dopamine releasing agents.

The most commonly prescribed indirect agonists of dopamine receptors include:

Other examples include:

See also

References

  1. ↑ Möller D, Banerjee A, Uzuneser TC, Skultety M, Huth T, Plouffe B, Hübner H, Alzheimer C, Friedland K, Müller CP, Bouvier M, Gmeiner P (2017). "Discovery of G Protein-Biased Dopaminergics with a Pyrazolo[1,5-a]pyridine Substructure". J. Med. Chem. 60 (7): 2908–2929. PMID 28248104. doi:10.1021/acs.jmedchem.6b01857.
  2. ↑ Hübner H, Schellhorn T, Gienger M, Schaab C, Kaindl J, Leeb L, Clark T, Möller D, Gmeiner P (2016). "Structure-guided development of heterodimer-selective GPCR ligands". Nat Commun. 7: 12298. PMC 4963535 Freely accessible. PMID 27457610. doi:10.1038/ncomms12298.
  3. ↑ Xu W, Wang X, Tocker AM, Huang P, Reith ME, Liu-Chen LY, Smith AB, Kortagere S (2017). "Functional Characterization of a Novel Series of Biased Signaling Dopamine D3 Receptor Agonists". ACS Chem Neurosci. 8 (3): 486–500. PMID 27801563. doi:10.1021/acschemneuro.6b00221.
  4. 1 2 Conroy JL, Free RB, Sibley DR (2015). "Identification of G protein-biased agonists that fail to recruit β-arrestin or promote internalization of the D1 dopamine receptor". ACS Chem Neurosci. 6 (4): 681–92. PMC 5234767 Freely accessible. PMID 25660762. doi:10.1021/acschemneuro.5b00020.
  5. ↑ Park SM, Chen M, Schmerberg CM, Dulman RS, Rodriguiz RM, Caron MG, Jin J, Wetsel WC (2016). "Effects of β-Arrestin-Biased Dopamine D2 Receptor Ligands on Schizophrenia-Like Behavior in Hypoglutamatergic Mice". Neuropsychopharmacology. 41 (3): 704–15. PMC 4707817 Freely accessible. PMID 26129680. doi:10.1038/npp.2015.196.
  6. ↑ Clinical trial number NCT00334048 at ClinicalTrials.gov - "Treating Sexual Dysfunction From SSRI Medication: a Study Comparing Requip CR to Placebo"
  7. ↑ Youssef MA, van Wely M, Hassan MA, et al. (March 2010). "Can dopamine agonists reduce the incidence and severity of OHSS in IVF/ICSI treatment cycles? A systematic review and meta-analysis". Hum Reprod Update. 16 (5): 459–66. PMID 20354100. doi:10.1093/humupd/dmq006.
  8. ↑ "MedlinePlus Drug Information: Pramipexole (Systemic)". United States National Library of Medicine. Archived from the original on 2006-09-26. Retrieved 2006-09-27.
  9. ↑ Boyd, Alan (1995). "Bromocriptine and psychosis: A literature review". Psychiatric Quarterly. 66 (1): 87–95. PMID 7701022. doi:10.1007/BF02238717. Retrieved 2008-09-06.
  10. ↑ Yeung EYH, Cavanna AE (2014). "Sleep Attacks in Patients With Parkinson's Disease on Dopaminergic Medications: A Systematic Review". Movement Disorderes Clinical Practice. 1 (4): 307–316. doi:10.1002/mdc3.12063.
  11. ↑ Nirenberg MJ (2013). "Dopamine agonist withdrawal syndrome: implications for patient care". Drugs Aging. 30 (8): 587–92. PMID 23686524. doi:10.1007/s40266-013-0090-z.
  12. ↑ Seeman P, Guan HC, Hirbec H (2009). "Dopamine D2High receptors stimulated by phencyclidines, lysergic acid diethylamide, salvinorin A, and modafinil". Synapse 63 (8): 698–704. doi:10.1002/syn.20647. PMID 19391150.
  13. ↑ FDA Announces Voluntary Withdrawal of Pergolide Products
  14. ↑ Matera, Carlo; Quadri, Marta; Pelucchi, Silvia; Amici, Marco De; Dallanoce, Clelia (2014-07-01). "A convenient synthesis of 4-(2-hydroxyethyl)indolin-2-one, a useful intermediate for the preparation of both dopamine receptor agonists and protein kinase inhibitors". Monatshefte für Chemie - Chemical Monthly. 145 (7): 1139–1144. ISSN 0026-9247. doi:10.1007/s00706-014-1211-z.
  15. ↑ Ng SS, Pang CC (March 2000). "In vivo venodilator action of fenoldopam, a dopamine D(1)-receptor agonist". Br. J. Pharmacol. 129 (5): 853–8. PMC 1571905 Freely accessible. PMID 10696081. doi:10.1038/sj.bjp.0703119.

6. Avanzi M, Uber E, Bonfa F. Pathological gambling in two patients on dopamine replacement therapy for Parkinson’s disease. Neurol Sci 2004; 25:98–101[Medline]

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