What are common dopamine antagonists?

Common Dopamine Antagonists

Common dopamine antagonists include typical antipsychotics (haloperidol, chlorpromazine), atypical antipsychotics (olanzapine, clozapine, risperidone), antiemetics (metoclopramide, prochlorperazine), and certain dopaminergic agents used for movement disorders (ropinirole, pramipexole). 1

Classification of Dopamine Antagonists

Typical (First-Generation) Antipsychotics

• High-potency agents:
  • Haloperidol
  • Fluphenazine
  • Trifluperazine
  • Pimozide
• Low-potency agents:
  • Chlorpromazine
  • Thioridazine

Atypical (Second-Generation) Antipsychotics

• Clozapine
• Olanzapine
• Quetiapine
• Risperidone
• Ziprasidone
• Sertindole

Antiemetics with Dopamine Antagonist Properties

• Metoclopramide
• Prochlorperazine
• Promethazine
• Droperidol
• Domperidone 1

Mechanism of Action

Dopamine antagonists work primarily by blocking dopamine receptors, particularly the D2 receptor subtype. Their effects vary based on:

1. Receptor binding affinity: How strongly they bind to dopamine receptors
2. Receptor selectivity: Which dopamine receptor subtypes they target
3. Dissociation rate: How quickly they detach from receptors 2

Key Differences Between Typical and Atypical Antipsychotics

• Typical antipsychotics bind more tightly than dopamine itself to D2 receptors and dissociate very slowly (over 30 minutes)

• Atypical antipsychotics bind more loosely than dopamine to D2 receptors and dissociate rapidly (less than 60 seconds) 2

• Atypical antipsychotics also act as serotonin-dopamine receptor antagonists, which contributes to their improved side effect profile 1

Clinical Applications

1. Psychiatric Disorders

• Schizophrenia
• Bipolar disorder
• Psychosis
• Agitation

2. Antiemetic Use

• Chemotherapy-induced nausea and vomiting
• Postoperative nausea and vomiting
• Radiation-induced nausea 1

3. Gastrointestinal Disorders

• Metoclopramide for gastroparesis and GERD (increases gastric motility) 3

4. Movement Disorders

• Restless Legs Syndrome (RLS) - dopamine agonists like ropinirole and pramipexole are first-line treatments 1

Common Side Effects

Extrapyramidal Symptoms (EPS)

• Acute dystonia
• Akathisia (restlessness)
• Parkinsonism
• Tardive dyskinesia (with long-term use) 4

Neuroendocrine Effects

• Hyperprolactinemia
• Galactorrhea
• Sexual dysfunction 2

Cardiovascular Effects

• Orthostatic hypotension
• QT prolongation (especially with certain agents)

Other Effects

• Sedation
• Anticholinergic effects (dry mouth, constipation, blurred vision)
• Weight gain (especially with atypical antipsychotics like olanzapine) 5

Clinical Pearls and Pitfalls

Important Considerations

1. Extrapyramidal symptoms are more common with typical antipsychotics and high-potency agents 1
2. Neuroleptic malignant syndrome is a rare but potentially fatal complication
3. Adverse effects of dopamine antagonists are often misdiagnosed as functional psychiatric disorders 4
4. Atypical antipsychotics generally have lower risk of EPS but higher risk of metabolic effects

Special Populations

• Elderly patients are more sensitive to side effects and should receive lower doses
• Pregnant patients may require antiemetics like metoclopramide when benefits outweigh risks
• Patients with Parkinson's disease should avoid dopamine antagonists when possible as they may worsen motor symptoms 1

Monitoring Recommendations

• Regular assessment for extrapyramidal symptoms
• Monitoring for tardive dyskinesia with long-term use
• Metabolic monitoring (weight, glucose, lipids) with atypical antipsychotics
• ECG monitoring for QT prolongation with certain agents

By understanding the different classes of dopamine antagonists and their unique properties, clinicians can select the most appropriate agent based on the clinical situation while minimizing adverse effects.