Determination of dopamine D2 receptor occupancy by lurasidone using positron emission tomography in healthy male subjects

Abstract

In healthy volunteers, single doses of lurasidone 40-80 mg resulted in D₂ receptor occupancy levels of >60%, a level of receptor occupancy previously associated with clinical response for atypical antipsychotics.

D2receptor occupancy following lurasidone treatment in patients with schizophrenia or schizoaffective disorder

“…regions examined. These results are consistent with Wong et al, 20 who found significant correlations between both serum lurasidone and metabolite ID-14283 with D 2 receptor occupancy in healthy male volunteers after a single dose (10-80 mg).…”

Assessment of Similarity in Antipsychotic Exposure‐Response Relationships in Clinical Trials Between Adults and Adolescents With Acute Exacerbation of Schizophrenia

“…The empirical use of the E max model is based on the ligand binding theory and is therefore justified in this analysis by the fact that inhibition of dopamine receptors induces a direct clinical response . Adult and adolescent parameter estimates for EC 50 appear to be in the range of inhibitory constant values (defined as the concentration required to produce 50% of maximum inhibition) reported in the literature …”

Management of bipolar I depression: clinical utility of lurasidone

“… 36 Receptor binding in humans as measured by positron emission tomography (PET) reveals that doses below 40 mg do not achieve adequate D 2 binding for an antipsychotic effect (41%–43% for 10 mg, and 51%–55% for 20 mg). 38 , 39 With a 40 mg dose the D 2 binding is 63%–67%, and increases to 77%–79% with 60 mg. Interestingly, higher doses do not increase receptor occupancy (73%–79% with 80 mg dose). 39 This observation may explain why Parkinsonism and elevated prolactin are uncommon with lurasidone in these studies, particularly with lower doses.…”

“… 38 , 39 With a 40 mg dose the D 2 binding is 63%–67%, and increases to 77%–79% with 60 mg. Interestingly, higher doses do not increase receptor occupancy (73%–79% with 80 mg dose). 39 This observation may explain why Parkinsonism and elevated prolactin are uncommon with lurasidone in these studies, particularly with lower doses. 31 However, D 2 receptor occupancy is more closely related to blood levels than to dosage of lurasidone, because of the significant variability in drug concentrations across individuals.…”