Rapid dissociation from the D2 receptor allows periodic accommodation of endogenous dopamine, causing less EPS. This is known as which theory?

Rapid dissociation from the D2 receptor allows periodic accommodation of endogenous dopamine, causing less EPS. This is known as which theory?

• A. Receptor dissociation
• B. Fast-off D2 theory
• C. Dopamine buffering
• D. EPS minimization

Answer: (B)

D2 receptor occupancy kinetics matter for both efficacy and side effects. When an antipsychotic dissociates from the D2 receptor rapidly, endogenous dopamine can occupy the receptor again during the brief intervals when the drug is not bound. This lets dopamine signal through the receptor in a pulsatile way, reducing continuous blockade in the nigrostriatal pathway and thus lowering extrapyramidal symptoms, while still suppressing excessive dopamine signaling that contributes to psychosis. This selective, rapid-off binding pattern is described by the fast-off D2 theory. Other ideas like generic receptor dissociation or broader concepts such as dopamine buffering don’t specifically capture the rapid off-rate that directly accounts for the reduced EPS seen with this mechanism.

D2 receptor occupancy kinetics matter for both efficacy and side effects. When an antipsychotic dissociates from the D2 receptor rapidly, endogenous dopamine can occupy the receptor again during the brief intervals when the drug is not bound. This lets dopamine signal through the receptor in a pulsatile way, reducing continuous blockade in the nigrostriatal pathway and thus lowering extrapyramidal symptoms, while still suppressing excessive dopamine signaling that contributes to psychosis. This selective, rapid-off binding pattern is described by the fast-off D2 theory. Other ideas like generic receptor dissociation or broader concepts such as dopamine buffering don’t specifically capture the rapid off-rate that directly accounts for the reduced EPS seen with this mechanism.