Biological Activity
AVN-492 is a very specific and highly-selective antagonist with picomolar affinity to 5-HT6R (Ki=91 pM).
In Vitro
The affinity of AVN-492 to bind to 5-HT6R (Ki=91 pM) is more than three orders of magnitude higher than that to bind to the only other target, 5-HT2BR, (Ki=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].
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.