Is haloperidol a dopamine antagonist?

Haloperidol is a Dopamine Antagonist

The correct answer is (c) haloperidol, which is a dopamine antagonist. Haloperidol is a traditional (typical) neuroleptic that exerts its antipsychotic properties through dopamine receptor blockade, specifically at D2 receptors 1.

Mechanism of Action of Haloperidol

• Haloperidol belongs to the class of traditional (typical) neuroleptics that function primarily as dopamine antagonists, specifically blocking D2 receptors 1
• This dopamine antagonism is the primary mechanism responsible for both its antipsychotic properties and its characteristic side-effect profile, including extrapyramidal symptoms 1
• Haloperidol binds more tightly than dopamine itself to the dopamine D2 receptor, with a dissociation constant lower than that of dopamine 2
• Unlike atypical antipsychotics, haloperidol has a slower dissociation rate from D2 receptors, remaining bound to these receptors for prolonged periods 2

Comparison with Other Answer Options

• Phentolamine (option a) is an alpha-adrenergic antagonist, not a dopamine antagonist 3
• Propofol (option b) is a GABA-modulating anesthetic agent, not a dopamine antagonist 3
• Clonidine (option d) is an alpha-2 adrenergic agonist, not a dopamine antagonist 3

Clinical Applications of Haloperidol

• Haloperidol is used in the treatment of schizophrenia and has been found superior to placebo in reducing symptoms of thought disorder, hallucinations, and persecutory ideation 1
• It is also used in the management of acute agitation and delirium, though recent guidelines suggest not routinely using haloperidol to treat delirium 1
• In pediatric populations, haloperidol has been studied for childhood-onset schizophrenia at doses of 0.02–0.12 mg/kg 1

Side Effects Related to Dopamine Antagonism

• Extrapyramidal symptoms are common side effects of haloperidol due to its dopamine antagonism and include:
  • Acute dystonia (involuntary muscle contractions) 1
  • Parkinsonism (bradykinesia, tremors, rigidity) 1
  • Akathisia (severe restlessness) 1
• Haloperidol can cause hyperprolactinemia due to the removal of dopamine's inhibitory effect on prolactin release 2
• QT prolongation is another concern with haloperidol, with a mean QT prolongation of approximately 7 ms 1

Pharmacological Distinctions

• Unlike atypical antipsychotics which have significant serotonergic (5-HT2A) antagonism, haloperidol's primary mechanism remains dopamine D2 antagonism 2
• Recent research suggests haloperidol may also have some effect on 5-HT3 receptors, though this is not its primary mechanism 4
• Chronic treatment with haloperidol leads to changes in striatal function beyond acute D2 receptor blockade, affecting both glutamatergic and GABAergic synaptic transmission 5

Clinical Considerations

• Haloperidol's dopamine antagonism occurs in both striatal and extrastriatal regions, with high D2 receptor blockade in the temporal cortex 6
• The antipsychotic threshold occupancy of D2 for therapeutic action is approximately 65%, while extrapyramidal symptoms typically emerge at occupancy levels above 80% 2
• Acute administration of haloperidol may initially enhance dopaminergic transmission due to presynaptic effects before establishing its therapeutic dopamine antagonism 7