5HT6-ligand-1

5HT6-ligand-1 is a potent 5-HT6 receptor ligand with a K_i of 1.43 nM. IC50 & Target: Ki: 1.43 nM (5-HT6)^[1] In Vivo: 5HT6-ligand-1 is extensively metabolized in rat liver microsomes whereas in human liver microsomes, 5HT6-ligand-1 is extensively metabolized (90%). The IC₅₀ values for 5HT6-ligand-1 at CYP 3A4 is 35.97%, whereas the IC₅₀ values at CYP 2D6 enzymes is less than 20 μM. 5HT6-ligand-1 at an oral dose of 10 mg/kg is rapidly absorbed in rats with a good oral half-life of 3.17±0.49 h with an oral bioavailability of 29±5%. The observed oral C_max is 60±44 ng/mL and occurs at 1.83 h. 5HT6-ligand-1 displays an oral exposure of 217±92 ng h/mL. It has a clearance of 220±92 mL/min/kg with a volume of distribution of 32.6±10.7 L/kg for iv dose. Extensive rat metabolism coupled with high clearance could be the possible reason for moderate oral bioavailability showed by 5HT6-ligand-1. Oral administration of 5HT6-ligand-1 reverses the time delay induced memory deficit and statistically significant effect is observed at a dose of 10 mg/kg indicating cognitive improvement potential of the compound 6a^[1].