Dopamine Antagonist Identification
Haloperidol is a dopamine antagonist that works primarily by blocking dopamine D2 receptors. 1
Mechanism of Action of the Options
Haloperidol
Haloperidol is a traditional neuroleptic that functions as a dopamine antagonist, specifically targeting D2 receptors. This dopamine antagonism is the primary mechanism responsible for its antipsychotic properties and also accounts for its characteristic side effect profile, including extrapyramidal symptoms 1. Haloperidol binds tightly to dopamine D2 receptors, with a dissociation constant lower than dopamine itself, and dissociates very slowly over time 2.
Other Options
- Phentolamine: An alpha-adrenergic antagonist, not a dopamine antagonist
- Propofol: An anesthetic that works primarily through GABA receptors, not dopamine antagonism
- Clonidine: An alpha-2 adrenergic agonist that reduces sympathetic outflow from the central nervous system 1
Clinical Applications of Haloperidol as a Dopamine Antagonist
Haloperidol's dopamine antagonism makes it effective for:
- Treatment of schizophrenia and psychotic disorders 1
- Management of acute agitation in emergency settings 1
- Control of nausea and vomiting, particularly in palliative care 1
Side Effects Related to Dopamine Antagonism
Haloperidol's dopamine blockade can cause:
- Extrapyramidal symptoms (EPS) including parkinsonism, akathisia, and dystonia 1
- Tardive dyskinesia with long-term use 1
- Hyperprolactinemia due to removal of dopamine's inhibitory effect on prolactin release 1
- Neuroleptic malignant syndrome in rare cases 1
- Cognitive impairment and negative effects on mood 3
Pharmacological Comparison with Atypical Antipsychotics
Unlike atypical antipsychotics which have looser binding to D2 receptors and often have significant serotonergic activity, haloperidol:
- Binds more tightly to D2 receptors 2
- Has a slower dissociation rate from D2 receptors 2
- Lacks significant serotonin 5-HT2A antagonism that characterizes many atypical agents 1
- May produce more oxidative stress in certain brain regions compared to some atypical antipsychotics 4, 5
Clinical Implications
Understanding haloperidol's mechanism as a dopamine antagonist is important because:
- It explains both its therapeutic efficacy and side effect profile
- It helps predict drug interactions with other agents affecting dopaminergic transmission
- It guides appropriate monitoring for adverse effects related to dopamine blockade
- It informs the selection of appropriate patients for whom the benefits outweigh the risks
In summary, of the options presented, haloperidol is definitively identified as a dopamine antagonist based on its well-established pharmacological profile and mechanism of action.