Development of a presynaptic 5-HT1A antagonist.

Abstract A new 5-HT 1A silent antagonist 14 (5-HT 1A IC 50 =2.2 nM) antagonizes the effects of agonists on reciprocal forepaw treading behavior, on neuronal firing in the rat dorsal raphe, and on 5-HT 1A release in the raphe and hippocampus. While 14 alone was inactive in the social interaction paradigm, it completely reversed the social interaction activity of the serotonergic compounds (buspirone, 1 , and 2 ).