Eptapirone

The affinity of Eptapirone for 5-HT1A binding sites (pKi, 8.33) is higher than that of buspirone (pKi, 7.50), and somewhat lower than that of flesinoxan (pKi, 8.91). In HeLa cells expressing human 5-HT1A receptors, Eptapirone decreases the forskolin-induced increase in AMP, and, based on its maximal effect, is found to have an intrinsic activity of 1.0 relative to that of 5-HT, which is significantly higher than that of buspirone (0.49), ipsapirone (0.46) and flesinoxan (0.93).^[1]

Cells are preincubated with DMEM, 10 mM HEPES for 10 min at room temperature. Drugs, at concentrations ranging from 0.1 nM to 100 M, and appropriate vehicle controls, are then added in DMEM, 10 mM HEPES, 100 M forskolin and 100 M IBMX to the cells. Antagonists are added at the same time as the agonists. At the end of the treatment (10 min, room temperature), the reaction is stopped by aspiration of the medium and addition of 0.1 N HCl. Cellular extract is diluted 1:500 or 1:400 in radioimmunoassay buffer, and cAMP content is measured by using a commercially available kit.

In vivo, Eptapirone (F11440) is 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). Eptapironeproduced anxiolytic- and antidepressant-like effects in animal models (i.e., increased punished responding in a pigeon conflict procedure and decreased immobility in a rat forced swimming test, respectively) that are more substantial than those of buspirone, ipsapirone and flesinoxan. ^[1]