AP521 is an agonist of the human 5-HT1A receptor (IC50: 94 nM).

5-HT1A receptor:94 nM

AP521 is an agonist of the human 5-HT1A receptor with IC50 values of 135 nM (5-HT1A, rat), 94 nM (5-HT1A, human), 254 nM (5-HT1B, rat), 5530 nM (5-HT1B, human), 418 nM (5-HT1D, human), 422 nM (5-HT5a, human), and 198 nM (5-HT7, rat). AP521 also reduces forskolin-induced cAMP accumulation from 10 nM to 10 μM.

AP521, at dosages ranging from 0.5 to 10 mg/kg, notably enhances shock acceptances and, when orally administered at 3 and 10 mg/kg, substantially reduces freezing time. Furthermore, it doubles the duration spent on the open arms compared to the vehicle-treated group, evidencing an anxiolytic-like effect that seems dose-dependent [F(3, 36)=4.21, P<0.05 for AP521]. At a concentration of 10 mg/kg, AP521 significantly boosts the extracellular 5-HT level in the medial prefrontal cortex (mPFC) from 0.5 to 1 hour post-administration. While a 3 mg/kg dose of AP521 suggests a potential increase in the extracellular 5-HT level, this rise is statistically insignificant.