Limbic selectivity of clozapine

Evaluation of Dopamine D-2 Receptor Occupancy by Clozapine, Risperidone, and Haloperidol In Vivo in the Rodent and Nonhuman Primate Brain Using 18F-Fallypride

“…This finding is similar to the higher temporal cortex D-2 occupancy (90%) compared to that in the striata (58%) reported in patients on clozapine and measured using a similar ratio method with 123 I-epidepride and SPECT (Pilowsky et al 1997). Measurement of receptor occupancy by the ratio method is confounded by at least two factors: (1) because of the different kinetic profile of 18 F-fallypride in the high versus low receptor concentration regions, the time at which pseudoequilibrium is achieved is different; and (2) the radiotracer likely reaches pseudoequilibrium in the drug challenge experiments at different times as compared to the control experiment and, therefore, measurement of occupancy using single time points may be difficult.…”

“…Using the ratio analysis similar to that reported by Pilowsky et al (1997), occupancy in the extrastriatal regions was found to be higher than striatal regions in the case of all the drugs, particularly for clozapine and risperidone. This finding is similar to the higher temporal cortex D-2 occupancy (90%) compared to that in the striata (58%) reported in patients on clozapine and measured using a similar ratio method with 123 I-epidepride and SPECT (Pilowsky et al 1997).…”

“…Results from in vivo imaging studies note that clozapine does not seem to increase occupancy of striatal D-2 receptors once it reaches a plateau of approximately 60%, unlike the Ͼ 80% occupancy observed with the other high-affinity neuroleptics (e.g., in Kapur et al 1999;Seeman and Tallerico 1999). In one report, a greater degree ( Ͼ 80%) of cortical D-2 receptor occupancy by clozapine has been reported using 123 I-epidepride and SPECT (Pilowsky et al 1997).…”

“…A number of studies have investigated the extent of occupancy of the dopamine D-2 receptors in vivo in the striata (caudate and putamen) by various neuroleptics in patients undergoing treatment (summarized recently in Seeman and Tallerico 1999). These studies have been carried out using positron emission tomography (PET with 11 Craclopride and 11 C-FLB 457 as the radioligand; for example, Farde et al 1994Farde et al , 1997Kapur et al 1999) as well as single photon emission tomography (SPECT using 123 I-IBZM and 123 I-epidepride; for example Kufferle et al 1997;Pickar et al 1996;Pilowsky et al 1997). All studies report a high degree of dopamine D-2 receptor occupancy (60 to 90%) by various typical and atypical drugs (Seeman and Tallerico 1999).…”

The Striatal and Extrastriatal D2/D3 Receptor-Binding Profile of Clozapine in Patients with Schizophrenia

“…However, the first studies in drug-treated schizophrenic patients performed with these ligands revealed controversial results with regard to the differential occupancy of striatal vs extrastriatal regions, which has been attributed to tracer characteristics and methodological pitfalls. Using [ 123 I]epidepride SPECT, Pilowsky et al (1997) demonstrated a higher occupancy of temporal cortical than striatal D 2 receptors by clozapine. This group reported the same observation for a number of other atypical antipsychotics (Bigliani et al, 2000;Bressan et al, 2003).…”