F-11440

A potent, selective 5-HT1A receptor agonist with Ki of 4.8 nM, pKi of 8.33; shows ≥shows 100-fold higher affinity for the other serotonin receptor subtypes, and has no detectable antidopaminergic activity and antihistaminergic activity; decreases the forskolin-induced increase in AMP in HeLa cells expressing human 5-HT1A receptors; produces anxiolytic- and antidepressant-like effects in animal models.Anxiety Phase 1 Discontinued (In Vitro) :The affinity of Eptapirone (F11440) for 5-HT1Abinding sites (pKi, 8.33) was higher than that of buspirone (pKi , 7.50), and somewhat lower than that of flesinoxan (pKi , 8.91) .In vivo, Eptapirone (F11440) was 4- to 20-fold more potent than flesinoxan, and 30- to 60-fold more potent than buspirone, in exerting 5-HT1A agonist activity at pre- and postsynaptic receptors in rats (measured by, for example, its ability to decrease hippocampal extracellular serotonin (5-HT) levels and to increase plasma corticosterone levels, respectively) . Eptapirone (F11440), shown here to be a potent, selective, high efficacy 5-HT1Areceptor agonist, appears to have the potential to exert marked anxiolytic and antidepressant activity in humans.