AVN-211

AVN-211 (CD-008-0173) is a selective and orally active 5HT₆R antagonist with an IC₅₀ of 2.34 nM and a K_i of 1.09 nM. AVN-211 exhibits 5K-fold higher 5HT₆R selectivity over other 65 receptors, enzymes, and ion channels. AVN-211 significantly improves cognitive and anxiety behaviors in various AD animal models, and has good safety profiles. AVN-211 can be used for the study of Alzheimer's dementia^[1]. In Vitro:AVN-211 (0.1-100 μM) significantly inhibits CYP2B6 (IC₅₀ = 0.76 μM), CYP2C9 (IC₅₀ = 2.68 μM), and CYP2C19 (IC₅₀ = 8.08 μM); it shows no significant inhibition on other CYP enzymes and its IC₅₀ for the hERG potassium channel with 18 μM^[1].
AVN-211 (17 μM and 500 ng/mL) exhibits high liver metabolic stability and plasma protein binding rate^[1].
In Vivo:AVN-211 (0.05-1 mg/kg, i.p. or 0.2 mg/kg, p.o., single dose) significantly reverses memory impairment, and its effect is superior to that of Memantine (HY-B0591) (5 mg/kg) and Tacrine (10 mg/kg) (HY-111338) in mice^[1].
AVN-211 (0.05-0.2 mg/kg, i.p., single dose) significantly improves the navigation ability of rats, restoring the dwell time in the target quadrant to a level close to that of the control group^[1].
AVN-211 (0.05-1 mg/kg, i.p., single dsose) extends the exploration time of the open arm, and its effect is comparable to that of Lorazepam, without causing motor inhibition^[1].
AVN-211 (0.05-0.2 mg/kg, i.p., single dose) restores the pre-pulse inhibition (PPI) to 46-55% in mice, confirming its potential as an antipsychotic agent^[1].
AVN-211 (500-20000 mg/kg, i.p., single dose or 1-400 mg/kg, p.o., for 180 days) exhibits acute toxicity LD₅₀ of 13684 mg/kg and there is no significant weight loss or organ damage in the long-term toxicity tests, no mutagenicity is observed in mice and rats, respectively^[1].