SB-277011 (hydrochloride)

SB-277011 hydrochloride (SB-277011A hydrochloride) is a potent, selective, orally bioavailable and brain penetrate?dopamine D₃?receptor (D₃R)?antagonist with K_i values of 10.7?nM and?11.2 nM?at?rodent and human?D₃R, respectively. SB-277011 hydrochloride displays 80- to 100-fold selectivity over other dopamine receptors with?pK_is of 8.0, 6.0, <5.2, and 5.9 for D3, D2, 5-HT_1B, and 5-HT_1D receptors, respectively^[1][2]. In Vivo: SB-277011 hydrochloride has an excellent pharmacokinetic profile, exhibits oral bioavailability 43%, half-life:2.0 h, plasma clearance 19 mL/min/kg) and to be highly brain-penetrant (brain:blood ratio of 3.6:1), with a clean P450 profile in the rat^[1].
SB-277011 hydrochloride (SB 277011; 3 mg/kg, p.o.) completely reverses the effects of quinelorane in the nucleus accumbens, but does not reverse the effects of quinelorane in the striatum at 93 mg/kg in rats^[1].
SB-277011 (intraperitoneal injection; 12.5-25 mg/kg) significantly and dose-dependently reduces intravenous cocaine self-administration under both low fixed-ratio and progressive-ratio reinforcement conditions in rats. When it increases to 50 mg/kg, SB-277011 can significantly inhibit basal and cocaine-enhanced locomotion in rats^[2].