SB-616234A is a selective and orally bioavailable 5-HT1B receptor antagonist, 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), and is over 100-fold selective for a range of molecular targets except h5-HT1D receptors (pKi 6.6 ± 0.1). Similarly, affinity (pKi) for rat and guinea pig striatal 5-HT1B receptors is 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 5-HT1/7 receptor agonist, 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]. SB-616234A (0.3-30 mg/kg p.o.) causes a dose-dependent inhibition of ex vivo [3H]-GR125743 binding to rat striatal 5-HT1B receptors with an ED50 of 2.83 ± 0.39 mg/kg p.o[1].
[1]. Lee A.Dawson, et al. Characterisation of the selective 5-HT1B receptor antagonist SB-616234-A (1-[6-(cis-3,5-dimethylpiperazin-1-yl)-2,3-dihydro-5-methoxyindol-1-yl]-1-[2′-methyl-4′-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methanone hydrochloride): In vivo neurochemical and behavioural evidence of anxiolytic/antidepressant activity. Neuropharmacology Volume 50, Issue 8, June 2006, Pages 975-983 [2]. Scott C, et al. SB-616234-A (1-[6-(cis-3,5-dimethylpiperazin-1-yl)-2,3-dihydro-5-methoxyindol-1-yl]-1-[2'methyl-4'-(5-methyl-1,2,3-oxadiazol-3-yl)biphenyl-4-yl]methanone hydrochloride): a novel, potent and selective 5-HT1B receptor antagonist. Neuropharmacology. 2006 Jun;50(8):984-90. Epub 2006 Mar 20.