ANXIOLYTIC PROPERTIES OF (+)-S-20499, A NOVEL SEROTONIN 5-HT1A FULL AGONIST, IN THE ELEVATED PLUS-MAZE AND SOCIAL-INTERACTION TESTS

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-HT1A 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 nmol/kg-1.9 mu mol/kg), (+) S 20499 (470 nmol/kg) or (-) S 20500 (94-940 nmol/kg) or per os administration of (+) S 20499 (190 nmol/kg-19 mu mol/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 nmol/kg-1.9 mu mol/ kg) or per os administration of (+) S 20499 (190 nmol/kg-19 mu mol/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. (C) Wiley-Liss, Inc.