TABLE 4

DAT occupancy of DAT inhibitors in rhesus monkey striatum: comparison with increased activity produced in parkinsonian monkeys DAT occupancy of DAT inhibitors was monitored by competition between the PET imaging agent and DAT inhibitor [¹¹C]CFT and candidate therapeutic DAT inhibitors. [¹¹C]CFT was injected via the i.v. route in normal rhesus monkeys to acquire baseline DAT levels by PET imaging. Images were acquired over the course of 1 h, followed by i.v. injection of the DAT candidate therapeutic. One hour later, [¹¹C]CFT was injected again, and images were acquired for 60 min, as outlined under Materials and Methods. Results are means ± S.E.M. of three to five independent experiments, with the exception of O-1014. The column designated `Improved Activity' indicates whether a DAT inhibitor increased activity at least 40% over baseline levels of activity, computed by calculating activity (measured by an accelerometer) for various times following injection of the test compound compared with baseline activity monitored 3 to 11 days before the drug testing day. Compounds designated `No' did not increase activity levels significantly for one or more days after administration.