Stimulus properties of arylpiperazines: NAN‐190, a potential 5‐HT_1A serotonin antagonist

Abstract

Abstract Arylpiperazines have been demonstrated to bind both at 5‐HT 1A and 5‐HT 1B serotonin receptors. In an attempt to design novel 5‐HT 1A agonists and antagonists, based on an arylpiperazine nucleus, we investigated the stimulus properties of a series of such agents (in rats trained to discriminate 0.5 mg/kg of the 5‐HT 1B agent TFMPP from saline) to determine what structural features were important for 5‐HT 1B activity. This done, we modified these agents to eliminate those features and, at the same time, incorporated structural features that appeared important for 5‐HT 1A affinity. The resulting agents displayed high affinity for 5‐HT 1A sites. One agent in particular, NAN‐190, neither mimicked nor antagonized the TFMPP stimulus, but was capable of antagonizing the stimulus produced by the 5‐HT 1A agonist 8‐OH DPAT (0.2 mg/kg). These preliminary results suggest that NAN‐190 may be a potential 5‐HT 1A antagonist.