Which group dissociates more slowly than clozapine and quetiapine?

• A. Aripiprazole
• B. Clozapine
• C. Asenapine, olanzapine, risperidone, ziprasidone
• D. Haloperidol

Answer: (C)

The main concept here is how quickly an antipsychotic lets go of the D2 receptor, because the dissociation rate (off-rate) from D2 influences how long the drug blocks dopamine signaling and how likely it is to cause extrapyramidal symptoms (EPS). Drugs that dissociate rapidly from the D2 receptor tend to produce fewer EPS; those that dissociate more slowly maintain receptor blockade longer and can cause more EPS.

Clozapine and quetiapine are known for rapid dissociation from D2 receptors, which helps explain their relatively low EPS profile. The group that includes asenapine, olanzapine, risperidone, and ziprasidone tends to have a slower dissociation from D2 receptors compared with clozapine and quetiapine, leading to longer receptor occupancy and a greater potential for EPS relative to clozapine/quetiapine (though still generally less than the classic slow-dissociating typical antipsychotics like haloperidol). This is why that group is identified as dissociating more slowly than clozapine and quetiapine.