AVN-101 is a highly potent 5-HT7 receptor antagonist with a Ki value of 153 pM. AVN-101 also exhibits considerable affinity for histamine H1 (Ki value of 0.58 nM) and adrenergic α2A, α2B and α2C (Ki values ​​of 0.41-3.6 nM) receptors. AVN-101 has shown good oral bioavailability and brain-blood barrier permeability, low toxicity and reasonable efficacy in animal models of central nervous system diseases.

α2B-adrenoceptor:0.41 nM (Ki), α2A-adrenoceptor:1.77 nM (Ki), H1:0.58 nM(Ki), 5-HT1A receptor:61 nM (Ki), α1A-adrenoceptor:18.9 nM (Ki), α2:0.41-3.6 nM(Ki), 5-HT2A receptor:1.56 nM (Ki), 5-HT6 receptor:2.04 nM (Ki), 5-HT7:153 pM(Ki), 5-HT2B receptor:10.6 nM (Ki), α1D-adrenoceptor:30.2 nM (Ki), α1B-adrenoceptor:9.4 nM (Ki), 5-HT1B receptor:720 nM (Ki), 5-HT2C receptor:1.17 nM (Ki), α2C-adrenoceptor:3.55 nM (Ki)

METHODS: The ability of AVN-101 to block hERG channels was tested in single-cell patch clamp experiments using HEK cells stably expressing hERG potassium channels and measuring potassium currents.
RESULTS Both AVN-101 and M1 blocked hERG channels with an IC50 score of 0.58 μM. [2]

METHODS: AVN-101 (5 mg/kg) was evaluated in Wistar rats when administered by oral (PO) and intravenous (I.v) routes. AVN-101 was detected in plasma using LC-MS/MS.
RESULTS The bioavailability of AVN-101 in rats (calculated based on AUC0 ⟶240 values) was 26.3% when injected intraperitoneally and 8.5% when administered orally. However, it should be noted that the drug elimination rate determined in the in vivo experiments, Kel = 0.0121 min-1 (i.v.), was significantly slower than that observed in rat microsomes (Kel = 0.335 min-1). [1]