SERUM AND CSF DRUG LEVELS AND D2 OCCUPANCY FOR PALIPERIDONE AND RISPERIDONE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Antagonism of the D2 family of dopamine receptors is critical for antipsychotic action and occupancy of central D2 receptors has been related a threshold for antipsychotic effect, as well as a threshold for extrapyramidal side effects (EPS). However, previous studies did not perform baseline measurements of D2 binding potential (Bmax) in the same cohort of patients, but rather relied on an age corrected estimate from a separate, mixed group of healthy subjects and drug na¿ve patients. In addition, the estimates for antipsychotic threshold were done for haloperidol, a first generation, typical antipsychotic with a high liability for EPS and for raclopride, a putative atypical antipsychotic which is not marketed in the United States, and the estimate for an EPS threshold was done only for haloperidol. It is important to determine these relationships in the newer atypical antipsychotics that currently form the mainstay of treatment for schizophrenia in the USA. Finally, PET scans of brain receptor occupancy are very expensive and require extensive patient cooperation. Thus, repeating these studies in new cohorts of patients, let alone using PET scans for guiding clinical treatment is not generally practical. In this study, we will relate central D2 receptor occupancy to serum blood level of drug in a nonhuman primate model.