Azaphen

Azaphen (Azafen) is an orally active tricyclic antidepressant that inhibits the reuptake of serotonin and monoamines, regulates the 5-HT2c receptor, and exerts sedative, antidepressant and anxiolytic effects. Azaphen increases the bioavailability of serotonin in the synaptic cleft, does not block muscarinic receptors or affect monoamine oxidase activity, and binds to the human serotonin transporter via salt bridges, π-stacking, π-cation and hydrophobic interactions. Azaphen can be used in studies related to depression^[1][2][3]. In Vitro:Azaphen (Azafen) (Less than 1 mg; 0.5 s exposure per frame, 2° s^-1 rotation rate, 120° total rotation angle) has its first atomic solid-state structure solved by MicroED at 0.82 Å resolution, revealing two inversion-related conformers with minimal conformational flexibility that supports binding to its target protein^[3].
Azaphen binds preferentially to the allosteric (S2) site of hSERT with minimal conformational change from its solid-state structure, stabilized by multiple key interactions including a salt bridge, pi-stacking, and pi-cation interactions^[3]. In Vivo:Azaphen (Azafen) (5-20 mg/kg; p.o.; single dose) exhibits pronounced antidepressant activity in the Porsolt behavioral despair test, with significant reductions in immobility duration at oral doses of 5, 10, and 20 mg/kg^[2].
Azaphen exhibits pronounced antidepressant activity in the Normura forced swimming test with significant reductions in depressive state duration^[2].