SB-224289 (hydrochloride)

SB-224289 hydrochloride is a selective 5-HT1B receptor antagonist, with anxiolytic effect. IC50 & Target: 5-HT1B receptor^[2] In Vitro: SB-224289 has specific toxin-blocking ability and does not inhibit Cho1p. SB-224289 (100 μM-25 μM) shows consistent efficacy at producing Pap-A resistance. SB-224289 does not directly inhibit the PS synthase enzyme in this in vitro assay. Moreover, SB-224289 specifically blocks the activity of papuamides and not other membrane disruptors. SB-224289 is unable to protect wild-type cells against KF, but it is able to provide protection against TPap-A^[1]. SB-224289 has a pK_i of 8 at human cloned 5-HT1B receptors and displays more than 80 fold selectivity over the closely related 5-HT1D receptor and a range of other receptors. SB-224289 is a potent antagonist with pEC₅₀ of 7.9±0.1. SB-224289 evokes a parallel rightward shift in the 5-HT concentration response curve with pA2 of 8.4±0.2. SB-224289 (100 nM and 1 μM) also significantly increases [³H]-5HT release in electrically stimulated guinea-pig brain cortex slices^[3]. In Vivo: SB-224289 (SB 224289) alone or in combination with cocaine, increases anxiety-like behavior. SB 224289 significantly reduces the amount of locomotor activity in the cocaine-treated rats. SB 224289-treated animals spend a significantly longer time in the corners than those treated with vehicle^[2]. SB 224289 is a potent antagonist with an ED₅₀ of 3.6 mg/kg, p.o in SK&F-99101-induced hypothermia in the guinea-pig. SB 224289 (4 mg/kg, p.o) reverses sumatriptan-induced inhibition of 5-HT release showing that it is also a potent terminal 5-HT autoreceptor antagonist in vivo. SB 224289 (2-16 mg/kg, p.o) does not increase 5-HT levels in the fuinea-pig frontal cortex. However, SB 224289 (4 mg/kg, p.o) causes a significantly increase in levels of 5-HT in the fuinea-pig dentate gyrus^[3].