Selective, potent, orally bioavailable full 5-HT1A antagonist. S-(+)-enantiomer of (±)-LY426965 is more active in comparison with its opposite enantiomer (R)-(-)-LY 426965. LY426965 completely reversed the effects of nicotine withdrawal on the auditory startle reflex in rats. In microdialysis experiments, LY426965, when administered with fluoxetine, significantly increased extracellular levels of serotonin above those achievable with fluoxetine alone. In electrophysiological studies, the administration of LY426965 both blocked and reversed the effects of fluoxetine on 5-HT neuronal activity. Preclinical results indicate that LY426965 may have clinical use as a pharmacotherapy for smoking cessation and depression and related disorders.