SB-616234-A is a selective and orally bioavailable antagonist of 5-HT1B receptor, with anxiolytic and antidepressant activity.

SB-616234A possesses high affinity for human 5-HT1B receptors stably expressed in Chinese hamster ovary (CHO) cells (pKi 8.3 ± 0.2). Similarly, rat and guinea pig striatal 5-HT1B receptors affinity (pKi) of 9.2 ± 0.1. In [35S]-GTPγS binding studies in the human recombinant cell line, SB-616234A acts as a high affinity antagonist with a pA2 value of 8.6 ± 0.2 whilst providing no evidence of agonist activity in this system. In [35S]-GTPγS binding studies in rat striatal membranes, SB-616234A acts as a high affinity antagonist with an apparent pKB of 8.4 ± 0.5, again whilst providing no evidence of agonist activity in this system. SB-616234A (1 μM) potentiates electrically stimulated [3H]-5-HT release from guinea pig and rat cortical slices (S2/S1 ratios of 1.8 and 1.6, respectively)[2].

SB-616234A reverses the agonist of 5-HT1/7 receptor, SKF-99101H-induced hypothermia in guinea pigs in a dose related manner with an ED50 of 2.4 mg/kg p.o. SB-616234A produces dose-related anxiolytic effects in both rat and guinea pig maternal separation-induced vocalisation models with an ED50 of 1.0 and 3.3 mg/kg i.p., respectively[1].a dose-dependent inhibition of ex vivo [3H]-GR125743 binding to rat striatal 5-HT1B receptors caused by SB-616234A (0.3-30 mg/kg p.o.) with an ED50 of 2.83 ± 0.39 mg/kg p.o[1].