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.
|Dopamine receptor agonist|
|Use||Parkinson's disease, Attention deficit hyperactivity disorder, restless legs syndrome, clinical depression, etc.|
|Biological target||Dopamine receptors|
Some medical drugs act as dopamine agonists and can treat hypodopaminergic (low dopamine) conditions; they are typically used for treating Parkinson's disease (PD), 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. 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).
- Pericardial effusion
- Fibrous thickening of lining that covers some of the internal organs including the heart or the lungs (fibrotic reaction)
- Causing or worsening psychosis
- Orthostatic hypotension
- Increased orgasmic intensity
- Weight loss
- Anorexia (symptom)
- Nausea and possible vomiting
- Unusual tiredness or weakness
- Possible Narcolepsy manifestations (Sleep attacks)
- Raynaud's phenomenon (common side effect of ergot derivatives)
- Twitching, twisting, or other unusual body movements
- Pathological addiction (gambling, shopping, internet pornography, hyper-sexuality) – specifically D3-preferring agonists
- After long-term use of dopamine agonists, a withdrawal syndrome may occur, during dose reduction or discontinuation, with the following possible side effects: anxiety, panic attacks, dysphoria, depression, agitation, irritability, suicidal ideation, fatigue, orthostatic hypotension, nausea, vomiting, diaphoresis, generalized pain, and drug cravings. For some individuals, these withdrawal symptoms are short-lived and make a full recovery, for others a protracted withdrawal syndrome may occur with withdrawal symptoms persisting for months or years.
Examples of dopamine agonists include:
- Aripiprazole (Partial agonist of the D2 family receptors - Trade name "Abilify" in the United States; atypical antipsychotic)
- Phencyclidine (a.k.a. PCP; partial agonist. Psychoactivity mainly due to NMDA antagonism)
- Quinpirole (Partial agonist of the D2 and D3 family of receptors)
- Salvinorin A (chief active constituent of the psychedelic herb salvia divinorum, the psychoactivity of which is mainly due to Kappa-opioid receptor agonism; partial agonist at the D2 with an Intrinsic activity of 40-60%, binding affinity of Ki=5-10nM and EC50=50-90nM)
Agonists of full/unknown efficacyEdit
- Apomorphine (Apokyn – used to treat Parkinson's disease/Restless leg syndrome) – G-protein bias at the D1 receptor.
- Bromocriptine (Parlodel – used to treat PD/RLS)
- Cabergoline (Dostinex – used to treat PD/RLS)
- Ciladopa (used to treat PD/RLS)
- Dihydrexidine (used to treat PD/RLS)
- Dinapsoline (used to treat PD/RLS)
- Doxanthrine (used to treat PD/RLS)
- Epicriptine (used to treat PD/RLS)
- Lisuride (used to treat PD/RLS)
- Pergolide (used to treat PD/RLS) – previously available as Permax, but removed from the market in the USA on March 29, 2007.
- Piribedil (Pronoran and Trivastal – used to treat PD/RLS)
- Pramipexole (Mirapex and Sifrol – used to treatPD/RLS)
- Propylnorapomorphine (used to treat PD/RLS)
- Quinagolide (Norprolac – used to treat PD/RLS)
- Ropinirole (Requip – used to treat PD/RLS)
- Rotigotine (Neupro – used to treat PD/RLS)
- Roxindole (used to treat PD/RLS)
- Sumanirole (used to treat PD/RLS)
The most commonly prescribed indirect agonists of dopamine receptors include:
- Amphetamine and/or dextroamphetamine (used to treat ADHD, narcolepsy, and obesity)
- Bupropion (used to facilitate smoking cessation and treat nicotine addiction and clinical depression)
- Lisdexamfetamine (used to treat ADHD and binge eating disorder)
- Methylphenidate or dexmethylphenidate (used to treat ADHD and narcolepsy)
Other examples include:
- 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. doi:10.1021/acs.jmedchem.6b01857. PMID 28248104.
- 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. doi:10.1038/ncomms12298. PMC . PMID 27457610.
- 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. doi:10.1021/acschemneuro.6b00221. PMID 27801563.
- Conroy, JL; Free, RB; Sibley, DR (April 15, 2015). "Identification of G protein-biased agonists that fail to recruit β-arrestin or promote internalization of the D1 dopamine receptor". ACS Chemical Neuroscience. 6 (4): 681–92. doi:10.1021/acschemneuro.5b00020. PMC . PMID 25660762. Retrieved September 28, 2017.
- 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. doi:10.1038/npp.2015.196. PMC . PMID 26129680.
- Clinical trial number NCT00334048 at ClinicalTrials.gov - "Treating Sexual Dysfunction From SSRI Medication: a Study Comparing Requip CR to Placebo"
- Youssef, Mohamed A.F.M.; van Wely, Madelon; Hassan, Mohamed Ahmed; Al-Inany, Hesham Gaber; Mochtar, Monique; Khattab, Sherif; van der Veen, Fulco (March 30, 2010). "Can dopamine agonists reduce the incidence and severity of OHSS in IVF/ICSI treatment cycles? A systematic review and meta-analysis". Human Reproduction Update. 16 (5): 459–66. doi:10.1093/humupd/dmq006. PMID 20354100. Retrieved September 28, 2017.
- "Pramipexole: MedlinePlus Drug Information". United States National Library of Medicine. Retrieved September 28, 2017.
- Boyd, Alan (March 1995). "Bromocriptine and psychosis: A literature review". Psychiatric Quarterly. 66 (1): 87–95. doi:10.1007/BF02238717. PMID 7701022. Retrieved September 28, 2017.
- Yeung, Eugene Y.H.; Cavanna, Andrea E. (September 1, 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. Retrieved September 28, 2017.
- Nirenberg, MJ (August 2013). "Dopamine agonist withdrawal syndrome: implications for patient care". Drugs & Aging. 30 (8): 587–92. doi:10.1007/s40266-013-0090-z. PMID 23686524. Retrieved September 28, 2017.
- 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.
- FDA Announces Voluntary Withdrawal of Pergolide Products
- Matera, Carlo; Quadri, Marta; Pelucchi, Silvia; Amici, Marco De; Dallanoce, Clelia (April 17, 2014). "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. 145 (7): 1139–1144. doi:10.1007/s00706-014-1211-z. ISSN 0026-9247. Retrieved September 28, 2017.
- Ng, Sylvia SW; Pang, Catherine CY (March 2000). "In vivo venodilator action of fenoldopam, a dopamine D(1)-receptor agonist". British Journal of Pharmacology. 129 (5): 853–8. doi:10.1038/sj.bjp.0703119. PMC . PMID 10696081.
- 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]