Eptapirone is a potent agonist of the serotonin (5-HT) receptor subtype 5-HT1A (Ki = 4.8 nM in a radioligand binding assay). It is selective for 5-HT1A over other 5-HT receptor subtypes, dopamine D2 receptors, α1-adrenergic receptors, and histamine H1 receptors (Kis = <10,000, 1,770, 691.8, and <10,000 nM, respectively). Eptapirone inhibits cAMP stimulation induced by forskolin in HA7 cells transfected with human 5-HT1A receptors (EC50 = 158 nM). In vivo, eptapirone increases extracellular 5-HT in the ventral hippocampus of rats (ED50 = 0.049 mg/kg) and serum corticosterone levels when administered p.o. or i.p. (ED50s = 0.16 and 0.057 mg/kg, respectively). It decreases immobility in rats in a forced swim test and increases punished responding in a pigeon conflict procedure, demonstrating antidepressant-like and anxiolytic activity. Eptapirone (2.5 mg/kg, p.o.) also attenuates hypertension and tachycardia induced by sibutramine in rats with no effect on sibutramine-induced hypophagia.
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