**Question:** Antipsychotic drug with least extra pyramidal side effect is:

A. Olanzapine
B. Quetiapine
C. Risperidone
D. Aripiprazole

**Core Concept:** Extrapyramidal side effects (EPSEs) are a group of symptoms that occur due to the blockade of D2 receptors in the extrapyramidal system. Antipsychotic drugs primarily target dopamine D2 receptors in the brain.

**Why the Correct Answer is Right:** Dopamine D2 receptors are primarily responsible for the antipsychotic action of antipsychotic drugs. However, excessive D2 receptor blockade can lead to EPSEs. Dopamine D2 receptors are widely distributed in the body, including the extrapyramidal system, which is responsible for involuntary movements and other EPS symptoms.

Dopamine D2 receptor blockade is dose-dependent. Among the given options, aripiprazole has the least affinity for D2 receptors compared to the other drugs. This means that aripiprazole requires higher doses to achieve therapeutic effects, resulting in reduced blockade of D2 receptors and lower risk of EPSEs.

**Why Each Wrong Option is Incorrect:**

A. Olanzapine: Olanzapine has a relatively high D2 receptor binding affinity, leading to a higher risk of EPSEs.
B. Quetiapine: Quetiapine has a similar affinity for D2 receptors as olanzapine, increasing the risk of EPSEs.
C. Risperidone: Risperidone has a high D2 receptor binding affinity, resulting in a higher risk of EPSEs.

**Clinical Pearl:** Extrapyramidal side effects are more likely to occur with drugs having a higher D2 receptor binding affinity. Aripiprazole, due to its unique pharmacology, has a lower risk of EPSEs compared to other atypical antipsychotics.