SB-222200 is an effective, selective, oral-active, BBB-permeable NK-3 receptor antagonist developed for CNS disease research. In vitro: inhibits ¹²⁵I-[MePhe⁷]NKB binding to CHO-hNK-3R (Ki 4.4 nM), antagonizes NKB-induced Ca²⁺ mobilization in HEK 293-hNK-3R (IC50 18.4 nM), selective for hNK-3 vs hNK-1 (Ki >100,000 nM) and hNK-2 (Ki 250 nM). In vivo: 5 mg/kg p.o. pretreatment inhibits senktide-induced behavioral responses in mice (57% inhibition); pharmacokinetics: rat T½ ~2 h, plasma clearance 56 mL/min/kg, Vd 3-5 L/kg; oral bioavailability 46% in rats (2.5 mg/kg i.v., 10 mg/kg p.o.).
