Eptapirone

Eptapirone (F-11,440) is a very potent and highly selective 5-HT1A receptor full agonist of the azapirone class. Its affinity for the 5-HT1A receptor is 4.8 nM (Ki) or 8.33 (pKi), and its intrinsic activity is 100% or equal to that of serotonin.

Eptapirone and its relatives such as F-13,640 and F-15,599 were developed under the notion that high receptor-activating efficacy is required for the maximal therapeutic benefits of 5-HT1A receptor agonists to be realized, underlying the poor clinical effectiveness of currently marketed agents like buspirone and tandospirone which act as mere weak-moderate partial agonists.

Rodent studies
In the forced swim test, eptapirone suppresses immobility more robustly than buspirone, ipsapirone, flesinoxan, paroxetine, and imipramine, indicating that it possesses powerful antidepressant effects which may be superior to those of currently available pharmaceuticals. In this test, unlike the other agents screened, buspirone actually increases immobility time with a single administration, while repeated administration decreases it, likely as a result of buspirone's very poor intrinsic activity (~30%) in activating the 5-HT1A receptor.

While high dose paroxetine is able to rival the reduction in immobility induced by eptapirone, it is only able to do so after repeated administration (in contrast to eptapirone which requires only a single dose), suggesting that eptapirone has a more rapid onset of action than other antidepressants as well. Imipramine was unable to match eptapirone or high dose paroxetine's efficacy as greater doses were fatal.

In the conflict procedure, eptapirone produces substantial increases in punished responding without affecting unpunished responding, demonstrating marked anxiolytic effects. Furthermore, these effects are more evident than those afforded by buspirone, ipsapirone, and flesinoxan.

Human studies
Eptapirone has been tested in humans in preclinical trials at an oral dose of 1.5 mg. In these studies, eptapirone reduces body temperature, suppresses REM sleep, increases cortisol and growth hormone levels, and produces side effects including dizziness and drowsiness while being overall well-tolerated. It peaks rapidly within 30–60 minutes and has an estimated half-life of two hours, with a total duration of approximately three hours.