Dopamine agonist

A dopamine agonist is a compound that activates dopamine receptors in the absence of that receptor's physiological ligand, the neurotransmitter dopamine. Dopamine agonists activate signaling pathways through the dopamine receptor and trimeric G-proteins, ultimately leading to changes in gene transcription.

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 Requip (Ropinirole) and Mirapex (Pramipexole) are FDA-approved for the treatment of RLS. There is also an ongoing clinical trial to test the effectiveness of the dopamine agonist Requip (ropinirole) in reversing the symptoms of SSRI-induced sexual dysfunction and Post-SSRI sexual dysfunction (PSSD).^[1] 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).^[2]

Side-effects

Some of the common side effects of dopamine agonists include:^[3][4]

• Euphoria
• Pericardial effusion
• Fibrous thickening of lining that covers some of the internal organs including the heart or the lungs (fibrotic reaction)
• Hallucinations
• Causing or worsening psychosis
• Orthostatic hypotension
• Increased orgasmic intensity
• Weight loss
• Anorexia (symptom)
• Nausea and possible vomiting
• Insomnia
• Unusual tiredness or weakness
• Dizziness
• Drowsiness
• Possible Narcolepsy manifestations (Sleep attacks)
• Lightheadedness
• Raynaud's phenomenon (common side effect of ergot derivatives)
• Syncope
• Twitching, twisting, or other unusual body movements
• Pathological addiction (gambling, shopping, internet pornography, hyper-sexuality) – specifically D₃-preferring agonists

Examples

Examples of dopamine agonists include:

Partial agonist

• 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 K_i=5-10nM and EC₅₀=50-90nM)^[5]

Agonists of full/unknown efficacy

• Apomorphine (Apokyn) (Dopamine Agonist for Parkinson's disease/Restless leg syndrome)
• Bromocriptine (Parlodel) (Dopamine Agonist for Parkinson's disease/Restless leg syndrome)
• Cabergoline (Dostinex) (Dopamine Agonist for Parkinson's disease/Restless leg syndrome)
• Ciladopa (Dopamine Agonist for Parkinson's disease/Restless leg syndrome)
• Dihydrexidine (Dopamine Agonist for Parkinson's disease/Restless leg syndrome)
• Dinapsoline (Dopamine Agonist for Parkinson's disease/Restless leg syndrome)
• Doxanthrine (Dopamine Agonist for Parkinson's disease/Restless leg syndrome)
• Epicriptine (Similar to those of Bromocriptine) (Dopamine Agonist for Parkinson's disease/Restless leg syndrome)
• Lisuride (Dopamine Agonist for Parkinson's disease/Restless leg syndrome)
• Pergolide (Dopamine Agonist for Parkinson's disease/Restless leg syndrome) (Permax) - Removed from the market in the USA March 29, 2007.^[6]
• Piribedil (Dopamine Agonist for Parkinson's disease/Restless leg syndrome)
• Pramipexole (Dopamine Agonist for Parkinson's disease/Restless leg syndrome) (Mirapex and Sifrol)
• Propylnorapomorphine (Dopamine Agonist for Parkinson's disease/Restless leg syndrome)
• Quinagolide (Norprolac) (Dopamine Agonist for Parkinson's disease/Restless leg syndrome)
• Ropinirole (Dopamine Agonist for Parkinson's disease/Restless leg syndrome) (Requip)
• Rotigotine (Dopamine Agonist for Parkinson's disease/Restless leg syndrome) (Neupro)
• Roxindole (Dopamine Agonist for Parkinson's disease/Restless leg syndrome)
• Sumanirole (Dopamine Agonist for Parkinson's disease/Restless leg syndrome)

Some, such as fenoldopam, are selective for dopamine receptor D1.^[7]

See also

• Dopamine antagonist
• Receptor agonist
• Dopaminergic
• Serotonin agonist
• Adrenergic agonist (Sympathomimetic)
• Histamine agonist
• Acetylcholine agonist (Parasympathomimetic)
• GABA agonist

References

1. ^ ClinicalTrials.gov NCT00334048 - "Treating Sexual Dysfunction From SSRI Medication: a Study Comparing Requip CR to Placebo"
2. ^ 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.  
3. ^ "MedlinePlus Drug Information: Pramipexole (Systemic)".  
4. ^ Boyd, Alan (1995). "Bromocriptine and psychosis: A literature review". Psychiatric Quarterly 66 (1): 87–95.  
5. ^ 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.
6. ^ FDA Announces Voluntary Withdrawal of Pergolide Products
7. ^ 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.  

• Dopamine Agonists at the US National Library of Medicine Medical Subject Headings (MeSH)
• http://www.abc.net.au/news/stories/2008/01/22/2143502.htm
• http://neuro.psychiatryonline.org/cgi/content/full/19/4/473