Dopamine antagonist

• Dopamine antagonists, also known as dopamine receptor antagonists, are a class of medications that block the action of dopamine at its receptors in the brain and other tissues.
• By inhibiting dopamine receptor activation, these agents produce various physiological effects.
• Dopamine antagonists are utilized in the management of several medical conditions, including psychotic disorders, nausea and vomiting, and certain gastrointestinal conditions.

Mechanism of Action

• Dopamine antagonists work by binding to dopamine receptors and preventing dopamine from activating these receptors.
• There are five main subtypes of dopamine receptors, D1 to D5, and dopamine antagonists may have varying affinities for these receptor subtypes.
• By blocking dopamine receptor activation, dopamine antagonists modulate dopaminergic neurotransmission, leading to a reduction in dopaminergic signaling in targeted regions of the brain and body.
• The specific effects of dopamine antagonists depend on the receptor subtype they interact with and their distribution in various tissues.
• Dopamine antagonists may produce different effects, including sedation, antiemesis (anti-vomiting), and antipsychotic actions.

Clinical Applications

• Dopamine antagonists have diverse applications in several medical conditions:

1. Psychotic Disorders

• Dopamine antagonists are a cornerstone in the treatment of psychotic disorders, such as schizophrenia and bipolar disorder. By blocking dopamine receptors in certain brain regions, these medications help alleviate positive symptoms of psychosis, such as hallucinations and delusions.

2. Nausea and Vomiting

• Certain dopamine antagonists are effective in managing nausea and vomiting, particularly in the context of chemotherapy-induced nausea, postoperative nausea, and motion sickness.
• They act on dopamine receptors in the brainstem and gut to reduce the sensation of nausea and inhibit the vomiting reflex.

3. Gastrointestinal Conditions

• Dopamine antagonists may be used in the treatment of certain gastrointestinal disorders, including gastroparesis (delayed gastric emptying) and gastroesophageal reflux disease (GERD).
• They help reduce symptoms like nausea and reflux by modulating gastrointestinal motility and reducing gastric acid secretion.

4. Tourette Syndrome

• In some cases, dopamine antagonists are employed to manage the tics and involuntary movements associated with Tourette syndrome.

Examples of Dopamine Antagonists

• Dopamine antagonists include a variety of medications, each with specific properties and clinical applications.

Some common examples of dopamine antagonists are:

• Haloperidol (Haldol): Haloperidol is a first-generation or typical antipsychotic medication used in the treatment of schizophrenia and other psychotic disorders. It primarily acts as a potent antagonist of D2 dopamine receptors, helping to reduce positive symptoms of psychosis such as hallucinations and delusions. Haloperidol is available in various formulations, including oral tablets and injectable solutions.
• Risperidone (Risperdal): Risperidone is a second-generation or atypical antipsychotic medication used to treat schizophrenia, bipolar disorder, and irritability associated with autism. It exerts its effects through antagonism of D2 and 5-HT2A (serotonin) receptors. Risperidone is available as oral tablets, orally disintegrating tablets, and long-acting injectable formulations.
• Aripiprazole (Abilify): Aripiprazole is a third-generation or atypical antipsychotic medication used in the management of schizophrenia, bipolar disorder, and major depressive disorder as an adjunct to antidepressants. It acts as a partial agonist at D2 and 5-HT1A (serotonin) receptors and as an antagonist at 5-HT2A receptors. Aripiprazole is available in oral tablets, orally disintegrating tablets, and long-acting injectable formulations.
• Metoclopramide (Reglan): Metoclopramide is a dopamine antagonist with prokinetic properties, primarily used to manage nausea, vomiting, and symptoms of gastroesophageal reflux disease (GERD). It acts as a D2 receptor antagonist in the chemoreceptor trigger zone, reducing the sensation of nausea and inhibiting the vomiting reflex. Metoclopramide is available in oral tablets and injectable formulations.
• Prochlorperazine (Compazine): Prochlorperazine is another dopamine antagonist used to treat nausea and vomiting, often in the context of chemotherapy-induced nausea, postoperative nausea, and vertigo. It is available in oral tablets, rectal suppositories, and injectable formulations.
• Promethazine (Phenergan): Promethazine is a dopamine antagonist with antihistaminic and anticholinergic properties, commonly used for the management of nausea and vomiting. It also has sedative effects and is sometimes used as a sleep aid. Promethazine is available in oral tablets, rectal suppositories, and injectable formulations.

Side Effects

• The use of dopamine antagonists can be associated with various side effects, which may vary depending on the specific agent, dose, and duration of therapy.

Common side effects include:

• Extrapyramidal Symptoms: Dopamine antagonists may lead to extrapyramidal symptoms, including parkinsonism-like effects such as rigidity, tremors, and bradykinesia (slowness of movement).
• Hyperprolactinemia: Some dopamine antagonists, particularly those with a higher affinity for D2 receptors, can increase prolactin levels, leading to symptoms such as galactorrhea (spontaneous milk production) and irregular menstruation.
• Sedation: Certain dopamine antagonists can cause sedation and drowsiness, particularly during the initial stages of treatment.
• Anticholinergic Effects: Dopamine antagonists with anticholinergic properties may produce dry mouth, blurred vision, constipation, and urinary retention.
• Metabolic Effects: Long-term use of some dopamine antagonists may be associated with metabolic changes, including weight gain and altered glucose and lipid levels.

• It's important for patients and healthcare providers to be aware of these potential side effects and weigh the benefits of treatment against the risks.

Contraindications

• Dopamine antagonists are contraindicated in certain medical conditions due to potential risks and adverse effects.

Contraindications include:

• Hypersensitivity: Patients with a known hypersensitivity to any dopamine antagonist or its components should avoid using these medications.
• Narrow-Angle Glaucoma: Dopamine antagonists with significant anticholinergic properties should be used with caution or avoided in patients with narrow-angle glaucoma, as they can exacerbate intraocular pressure.
• Severe Central Nervous System Depression: Dopamine antagonists can cause sedation and may exacerbate central nervous system depression in conditions such as coma or severe head injury.
• Prolactin-Dependent Tumors: Patients with prolactin-dependent tumors, such as prolactinomas, should not receive dopamine antagonists, as these medications may stimulate tumor growth and worsen symptoms.
• Phaeochromocytoma: Dopamine antagonists should be avoided in patients with phaeochromocytoma (adrenal gland tumor), as they can cause severe hypertension.

Drug Interactions

• Dopamine antagonists may interact with other medications, leading to altered drug levels or increased risk of side effects.

Some significant drug interactions include:

• Other Antipsychotic Medications: Concurrent use of multiple antipsychotic medications, including dopamine antagonists, can increase the risk of extrapyramidal symptoms and other adverse effects.
• Levodopa: When used together, dopamine antagonists can reduce the efficacy of levodopa in Parkinson's disease. However, they may be combined in certain situations to manage specific symptoms.
• Metoclopramide: Metoclopramide, a dopamine receptor antagonist with prokinetic properties, may antagonize the effects of other dopamine antagonists and should be used cautiously together.
• Antihypertensive Medications: Dopamine antagonists may interact with antihypertensive medications, leading to additive hypotensive effects. Dose adjustments may be necessary in such cases.
• Anticholinergic Medications: Concomitant use of multiple anticholinergic medications with dopamine antagonists may lead to additive anticholinergic effects, resulting in dry mouth, constipation, and other adverse reactions.

• It is crucial for healthcare providers to review a patient's medication history thoroughly to identify potential drug interactions before prescribing dopamine antagonists.

Conclusion

• Dopamine antagonists are essential therapeutic agents used in the management of various medical conditions, ranging from psychotic disorders to nausea and vomiting.
• By blocking dopamine receptor activation, these medications produce diverse effects, influencing dopaminergic neurotransmission in different regions of the brain and body.
• However, like all medications, dopamine antagonists can cause side effects, and individualized treatment plans and close monitoring are necessary to ensure optimal patient outcomes.
• As medical students, understanding the mechanism of action and clinical applications of dopamine antagonists will prepare you to contribute to their safe and effective use in patient care.

See Also

• Dopamine Agonists
• Schizophrenia
• Hyperprolactinemia

References

• Citrome L. Comparison of intramuscular ziprasidone, olanzapine, or aripiprazole for agitation: a quantitative review of efficacy and safety. J Clin Psychiatry. 2007 Jun;68(6):1876-85. doi: 10.4088/jcp.v68n1215. PMID: 17592905.
• Marder SR. A review of agitation in mental illness: treatment guidelines and current therapies. J Clin Psychiatry. 2006;67 Suppl 10:13-21. PMID: 16961423.
• Miller DD, McEvoy JP, Davis SM, et al. Clinical correlates of tardive dyskinesia in schizophrenia: baseline data from the CATIE schizophrenia trial. Schizophr Res. 2005;80(1):33-43. doi:10.1016/j.schres.2005.06.016.
• Seeman P, Caruso C, Lasaga M. Dopamine partial agonist actions of the antipsychotics eticlopride and bromperidol. Mol Psychiatry. 2008;13(12):1101-1112. doi:10.1038/mp.2008.53.
• U.S. Food and Drug Administration. HALDOL (haloperidol) Tablets. Full prescribing information. Revised April 2017. Available at: [1]
• U.S. Food and Drug Administration. REGLAN (metoclopramide) Tablets. Full prescribing information. Revised February 2020. Available at: [2]
• U.S. Food and Drug Administration. INVEGA (paliperidone) Extended-Release Tablets. Full prescribing information. Revised March 2021. Available at: [3]
• U.S. Food and Drug Administration. ABILIFY (aripiprazole) Tablets. Full prescribing information. Revised March 2021. Available at: [4]
• U.S. Food and Drug Administration. COMPAZINE (prochlorperazine) Tablets. Full prescribing information. Revised August 2018. Available at: [5]
• U.S. Food and Drug Administration. PHENERGAN (promethazine hydrochloride) Tablets and Suppositories. Full prescribing information. Revised October 2014. Available at: [6]

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