SR 57227A

SR 57227A is a potent, orally active and selective 5-HT3 receptor agonist, with ability to cross the blood brain barrier. SR 57227A has affinities (IC₅₀) varying between 2.8 and 250 nM for 5-HT3 receptor binding sites in rat cortical membranes and on whole NG 108-15 cells or their membranes. Anti-depressant effects^[1][2]. In Vitro: SR 57227A binds to 5-HT3 receptors labelled with [3H]S-zacopride with an affinity (K_i) of 115 nM in rat cerebral cortex, 150 nM in NG 108-15 cell membranes and 103 nM in whole NG 108-15 cell^[1]. In Vivo: SR 57227A (1-30 mg/kg; i.p.) dose-dependently reduces immobility time in the forced swimming test with an ED₅₀ value for this effect of 14.2 mg/kg^[2].
In the forced swimming test, SR 57227A dose-dependently reduces the duration of immobility in rats after i.p. administration. (ED₅₀=7.6 mg/kg i.p. in rats.) SR 57227A is also active in both species after oral administration. In a time-course study in mice, SR 57227A (20 mg/kg p.o.) produces a significant effect lasting 6 hours. SR 57227A (1 and 3 mg/kg i.p.) reduces the elevation of the escape failures in the learned helplessness model in rats by 50-60% on the last two days of the avoidance task, and reduces isolation-induced aggressivity in mice by 50 to 85%, an effect which is antagonised by Zacopride (1 mg/kg i.p.)^[2].