Reply to "Intrinsic Activity of Aripiprazole Is Not 30% of Dopamine, But Only About 6% Under Ideal Antipsychotic Therapy"

Letter to the Editor

Sir: I appreciate the letter from Drs. Hamamura, Kodama,and Harada but must respectfully disagree with their argumentas follows:
Dr. Hamamura and colleagues suggest that the intrinsic activityof a partial receptor agonist is derived mathematicallyfrom the percentage of the target receptor occupied by differentdoses of the partial agonist versus the percentage of that receptoroccupied by its endogenous agonist under normal physiologicconditions. Instead, the intrinsic activity of a partialagonist is determined by measuring its maximal functional effecton its target receptor versus the maximal functional effectof the endogenous agonist of the same receptor. Admittedly,there should be some agreement between these 2 different conceptssince the latter is a major determinant of the former.