Schizophrenia What Is a Dopamine Agonist? By Adrian Preda, MD Adrian Preda, MD LinkedIn Adrian Preda, MD, is a board-certified psychiatrist with specialties in adult and geriatric psychiatry and clinical neuropsychiatric research. Learn about our editorial process Updated on March 08, 2022 Medically reviewed Verywell Mind articles are reviewed by board-certified physicians and mental healthcare professionals. Medical Reviewers confirm the content is thorough and accurate, reflecting the latest evidence-based research. Content is reviewed before publication and upon substantial updates. Learn more. by Daniel B. Block, MD Medically reviewed by Daniel B. Block, MD LinkedIn Twitter Daniel B. Block, MD, is an award-winning, board-certified psychiatrist who operates a private practice in Pennsylvania. Learn about our Medical Review Board Print Table of Contents View All Table of Contents Definition Dopamine Agonists vs. Antagonists Types of Dopamine Agonists Uses Impact Potential Pitfalls What Is a Dopamine Agonist? A dopamine agonist is a type of medication that binds to dopamine receptors in the brain and mimics the actions of dopamine. Dopamine is an important neurotransmitter that plays a role in a variety of mental functions. Dopamine levels can have an impact on mood, memory, and behavior. Dopamine agonists are sometimes used to treat disorders linked to problems with dopamine, including schizophrenia and bipolar disorder. This article will explain how dopamine agonists are used to treat psychotic conditions. This effect is best illustrated by Abilify (aripiprazole) and Rexulti (brexipiprazole). These second-generation antipsychotic/atypical neuroleptics are different from all the other atypical antipsychotics because of how they work. Dopamine Agonists vs. Antagonists Dopamine is one of the neurotransmitters found in the synaptic space, which is the space between neurons (nerve cells). Dopamine is released into the synaptic space from vesicles housed in the pre-synaptic neuron. These chemicals then bind to dopamine receptors in the postsynaptic neuron. Think of this as a key and lock type of effect: Dopamine receptors are locks that open when the dopamine “key” enters the lock. One explanation for schizophrenia is that there is too much dopamine in the synapses in certain parts of the brain. The positive symptoms of schizophrenia are thought to be a result of all these “extra” dopamine molecules. Dopamine Antagonists Some antipsychotic medications work as dopamine antagonists. They bind to the dopamine receptors, thus blocking dopamine from binding to the post-synaptic cell. And without the proper key, i.e. dopamine, the lock does not open. This prevents excess dopamine activity and helps relieve some of the symptoms of schizophrenia. The problem with this approach is that the dopamine blockade occurs all over the brain, while the dopamine excess in schizophrenia is limited to specific parts of the brain. Further, in schizophrenia, while some parts of the brain are subject to dopamine excess, other parts are in fact experiencing a dopamine deficit. Dopamine antagonists do not only block dopamine receptors in places where there is too much of it but also in places where there is not enough dopamine. Dopamine antagonists are effective for positive symptoms because they block receptors in brain regions that have too much dopamine. But this is why these medications tend to also increase negative symptoms, cognitive issues, and other side effects in patients taking them. Dopamine Partial Agonists A potential solution is to use partial agonists. A dopamine partial agonist is a molecule that binds to the receptor and partially activates it. Think about it as a key that sort of fits in the lock so that the door can be wriggled about but not completely opened. The effect of a dopamine partial agonist is less than the full effect but more than a complete lack of effect, which is what happens when a receptor is completely blocked. In other words, a partial effect. A dopamine partial agonist such as aripiprazole reduces the effect of excess dopamine by taking up space on the dopamine receptors. Because the receptors are only partially activated, dopamine activity is minimized. In situations when there is too little dopamine to activate all the available receptors, aripiprazole will actually bind to unoccupied receptors and mimic its effect, even if only partially. This can help add to the dopamine effect in synapses that were previously dopamine-deprived. Depending on a person's existing dopamine levels, a dopamine agonist medication such as aripiprazole may act as a full antagonist, a moderate antagonist, or a partial agonist. Recap Dopamine partial agonists, such as aripiprazole, act as a modulator of dopamine effects. When present, these medications diminish the effects of both dopamine excess (by decreasing dopamine action when there is too much of it) and deficit (by increasing dopamine action when there is too little of it). Types of Dopamine Agonists Antipsychotic medications that act as dopamine agonists are: Abilify (aripiprazole)Rexulti (brexipiprazole) The majority of second-generation (atypical) antipsychotics block the D-2 (dopamine-2) receptors but also block serotonin receptors. Serotonin is another neurotransmitter involved in mood. Second-generation antipsychotics such as Risperdal (risperidone), Geodon (ziprasidone), and Invega (paliperidone) are all potent antagonists of dopamine D2 receptors, while Clozaril (clozapine) and Seroquel (quetiapine) are weak D2 antagonists. Other Types of Dopamine Agonists There are also other types of dopamine agonist medications that may be prescribed to treat medical conditions linked to dopamine activity. For example, some dopamine agonist medications may be helpful in the treatment of Parkison's disease and restless leg syndrome. Research has also found that cannabidiol (CBD) acts as a dopamine partial agonist and may have antipsychotic effects. Uses of Dopamine Agonists Because these medications modulate dopamine activity, they can be useful in the treatment of psychiatric conditions including schizophrenia and bipolar disorder. These conditions are associated with too much dopamine activity. Excessive dopamine action can cause certain areas of the brain to become overactive, which is believed to play a role in symptoms such as delusions and hallucinations. The FDA has also approved aripiprazole in the treatment of other conditions including mixed episodes of bipolar disorder, long-term treatment of bipolar disorder, adjunctive treatment of major depression, Tourette's syndrome, and symptoms of irritability associated with autism. It is also sometimes prescribed off-label to treat borderline personality disorder and elevated prolactin levels that may occur when taking other antipsychotic medications. Impact of Dopamine Agonists Dopamine agonists may help relieve common symptoms of schizophrenia including hallucinations, delusions, and disorganized thinking. Research suggests that aripiprazole is as effective as other antipsychotic medications in the treatment of schizophrenia. A benefit of this medication is that it is less likely to produce extrapyramidal side effects than typical antipsychotics. It is also less likely to produce metabolic changes than other atypical antipsychotic medications. What Are Extrapyramidal Side Effects? Extrapyramidal side effects are involuntary movements that sometimes occur when taking antipsychotic medication. They are less likely to occur with some types of medications, but all antipsychotics can potentially produce these side effects. Potential Pitfalls Dopamine agonists can still have side effects and other adverse reactions. Some potential side effects include: Constipation Drowsiness Extrapyramidal symptoms (EPS) include akathisia, dystonia, parkinsonism, and tardive dyskinesia Headaches Increased glucose With aripiprazole, the risk for certain neurological adverse effects such as episodes of acute muscular rigidity (dystonia) or involuntary abnormal movement disorders (dyskinesia) is low. This can be contrasted with antipsychotics that have a high risk for these adverse effects, which are classified as typicals. Recap Typical antipsychotics work by blocking the majority of the D2 dopamine receptors, whereas atypical antipsychotics affect dopamine receptors as well as some serotonin receptors. While partial agonists such as aripiprazole have a better safety profile, people may experience side effects while taking these medications. Summary Dopamine agonists such as Abilify and Rexulti can be an effective option in the treatment of schizophrenia. These medications work by affecting dopamine receptors to help modulate dopamine levels in the body. This may help relieve some psychotic symptoms such as hallucinations, delusions, and disorganized thinking. These medications are also less likely to cause extrapyramidal symptoms than other types of antipsychotics due to their mechanism of action. 5 Sources Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy. Seeman P. Cannabidiol is a partial agonist at dopamine D2High receptors, predicting its antipsychotic clinical dose. Transl Psychiatry. 2016;6(10):e920-e920. doi:10.1038/tp.2016.195 National Alliance on Mental Illness. Aripiprazole (Abilify). Ribeiro ELA, de Mendonça Lima T, Vieira MEB, Storpirtis S, Aguiar PM. Efficacy and safety of aripiprazole for the treatment of schizophrenia: an overview of systematic reviews. Eur J Clin Pharmacol. 2018;74(10):1215-1233. doi:10.1007/s00228-018-2498-1 FDA. Highlights of prescribing information: Abilify. Divac N, Prostran M, Jakovcevski I, Cerovac N. Second-generation antipsychotics and extrapyramidal adverse effects. BioMed Res Int. 2014;2014:1-6. doi:10.1155/2014/656370 By Adrian Preda, MD Adrian Preda, MD, is a board-certified psychiatrist with specialties in adult and geriatric psychiatry and clinical neuropsychiatric research. See Our Editorial Process Meet Our Review Board Share Feedback Was this page helpful? Thanks for your feedback! What is your feedback? Other Helpful Report an Error Submit Speak to a Therapist Online Advertiser Disclosure × The offers that appear in this table are from partnerships from which Verywell Mind receives compensation.