AVN-492

1220646-23-0

C17H21N5O2S

DMSO : >= 100 mg/mL (278.20 mM)

Neuronal Signaling; GPCR/G Protein

AVN-492 is a very specific and highly-selective antagonist with picomolar affinity to 5-HT6R (K_i=91 pM). IC50 & Target: Ki: 91 pM (5-HT6R)^[1] In Vitro: The affinity of AVN-492 to bind to 5-HT6R (K_i=91 pM) is more than three orders of magnitude higher than that to bind to the only other target, 5-HT2BR, (K_i=170 nM). Thus, AVN-492 displays great 5-HT6R selectivity against all other serotonin receptor subtypes, and is extremely specific against any other receptors such as adrenergic, GABAergic, dopaminergic, histaminergic, etc^[1]. In Vivo: In rats, the plasma, brain, and CSF concentrations of the PO administered AVN-492 are dose-dependent. The drug concentration curves for the plasma and brain are of hyperbolic shape and at all doses the brain-plasma ratio is near 11%. The drug concentration in CSF, however, is nearly linearly dependent on the dose, reaching 50% of the plasma level at 10mg/kg. In mice, the plasma and brain concentrations of AVN-492, given IV at a dose of 2 mg/kg, decreased with time but at both time points, 15 min and 60 min, the brain/plasma ratio (mean+/-SEM) is nearly the same, at 13.2+/-0.7% and 9.0+/-1.5%, respectively. This indicates that the steady-state concentration gradient of AVN-492 is established by at least 15 min after the drug administration^[1].