Anxiolytic properties of (+) s 20499, a novel serotonin 5‐HT_1A full agonist, in the elevated plus‐maze and social interaction tests

Abstract

Abstract Previous studies have shown that (±) S 20244 (8‐(4‐[N‐(5‐methoxychroman‐3‐yl)N‐propylamino] butyl) 8‐azaspiro[4,5]decane‐7,9 dione) and its isomers (+) S 20499 and (−) S 20500 are full agonists at 5‐HT 1A receptors. In the present study, the effects of these three compounds were investigated in two animal models of anxiety, the elevated plus‐maze and social interaction tests. Subcutaneous administration of (±) S 20244 (19 μmol/kg−1.9 μmol/kg), (+) S 20499 (470 μmol/kg) or (−) S 20500 (94–940 μmol/kg) or per os administration of (+) S 20499 (190 μmol/kg−19 μmol/kg) produced anxiolytic‐like effects in the elevated plus‐maze while per os administration of (−) S 20500 was without effect. Subcutaneous administration of (±) S 20244 (19 μmol/kg−1.9 μmol/kg) or per os administration of (+) S 20499 (190 μmol/kg−19 μmol/kg) also produced anxiolytic‐like effects in the social interaction test. With both substances, bell‐shaped dose‐response relationships were found. The absence of activity of (−) S 20500 when administered per os suggests that the distribution and/or absorption kinetics of the two isomers may be different. In conclusion, (±) S 20244 and (+) S 20499 both display anxiolytic‐like activity in the elevated plus‐maze and social interaction tests.