Which antipsychotic drug acts primarily as a dopamine D₂ receptor partial agonist rather than an antagonist?

Explanation

## Dopamine Partial Agonism in Antipsychotics **Key Point:** Aripiprazole is a **partial agonist at dopamine D₂ receptors**, a unique mechanism distinct from all other antipsychotics which are D₂ antagonists. ### Mechanism of Action: Partial Agonism vs. Antagonism ```mermaid flowchart TD A[Dopamine at D₂ receptor]:::outcome --> B{Receptor occupancy strategy}:::decision B -->|Full antagonism| C[Block all D₂ signaling]:::action B -->|Partial agonism| D[Partial D₂ activation]:::action C --> E[Antipsychotic effect<br/>but EPS risk]:::outcome D --> F[Stabilize dopamine<br/>Low EPS & metabolic risk]:::outcome C --> G[Typical & most atypicals]:::outcome D --> H[Aripiprazole only]:::outcome ``` ### Clinical Implications of Partial Agonism | Feature | D₂ Antagonists (Other Antipsychotics) | Aripiprazole (Partial Agonist) | | --- | --- | --- | | **Mechanism** | Block all dopamine signaling | Provide baseline dopamine activity | | **EPS Risk** | Moderate to high | Very low | | **Weight Gain** | Moderate to high | Minimal | | **Metabolic Effects** | Significant | Minimal | | **Hyperprolactinemia** | Common | Rare | | **Efficacy** | Proven | Equivalent | **High-Yield:** Aripiprazole's partial agonism provides a "dopamine stabilizing" effect: - In **hyperactive dopaminergic states** (acute psychosis) → partial agonism reduces excess signaling - In **hypoactive dopaminergic states** (negative symptoms, depression) → partial agonism provides baseline activity **Clinical Pearl:** Aripiprazole is often used as a switch agent for patients experiencing metabolic side effects or extrapyramidal symptoms with other antipsychotics. It is also approved for augmentation in major depression. **Mnemonic:** **ARIP** = **A**gonist (partial), **R**educed side effects, **I**mproved **P**rofile. **Warning:** Do not confuse aripiprazole's partial agonism with inefficacy — it is equipotent to antagonists for antipsychotic efficacy but with a superior tolerability profile. [cite:Harrison 21e Ch 397]