Risperidone

The structures of PDM‐042 and [³H]PDM‐042 are shown in Figure 1A and B, respectively. PDM‐042 was synthesized in‐house and used as a free base in all experiments. [³H]PDM‐042 (662 GBq/mmol) was synthesized by Sekisui Medical Co., Ltd. (Tokyo, Japan). PDM‐042 was dissolved in dimethylsulfoxide and stored at −20°C to perform in vitro assays. PDM‐042 was suspended in 0.5% methylcellulose solution (Wako Pure Chemical Industries, Ltd., Osaka, Japan) and orally administered at a volume of 5 mL/kg in rats and 2 mL/kg in dogs. When PDM‐042 was intravenously (i.v.) administered at a volume of 1 mL/kg in the pharmacokinetic study, it was dissolved in 50% (v/v) N, N‐dimethylacetamide (Wako Pure Chemical Industries) and 50% (v/v) polyethylene glycol 400 (Wako Pure Chemical Industries). Risperidone (Toronto Research Chemicals Inc., Toronto, Canada) and olanzapine (U.S. Pharmacopeial Convention, Rockville, MD) were dissolved in minimal amounts of aqueous hydrochloric acid solution, diluted to the required concentrations with physiological saline, and subcutaneously administered at a volume of 1 mL/kg. MK‐801 ((5R,10S)‐(+)‐5‐methyl‐10,11‐dihydro‐5H‐dibenzo[a,d]cyclohepten‐5,10‐imine hydrogen maleate, Sigma‐Aldrich Co. LLC, St. Louis, MO) was dissolved in physiological saline and subcutaneously administered at a volume of 1 mL/kg.