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.
SR 57227A (1-30 mg/kg; i.p.) dose-dependently reduces immobility time in the forced swimming test with an ED
50
value for this effect of 14.2 mg/kg.
In the forced swimming test, SR 57227A dose-dependently reduces the duration of immobility in rats after i.p. administration. (ED
50
=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.).
