AVN-101 (hydrochloride)

AVN-101 hydrochloride is a potent, brain-penetrant and orally active 5-HT7 receptor antagonist (K_i of 153 pM), with slightly lesser potency toward 5-HT6, 5-HT2A, and 5HT-2C receptors (K_i values of 2.04 nM, 1.56  nM, and 1.17  nM, respectively). AVN-101 hydrochloride also exhibits a rather high affinity toward histamine H1 (K_i of 0.58 nM) and adrenergic α2A, α2B, and α2C (K_i= 0.41-3.6 nM) receptors. AVN-101 hydrochloride can be studied in such diseases as general anxiety disorders, depression, schizophrenia, Alzheimer’s disease, and multiple sclerosis^[1]. In Vitro:AVN-101 hydrochloride shows some ability to compete with radio-labeled ligands for both the histamine H1 (K_i  =  0.58 nM) and H2 receptors (K_i  =  89 nM) while being totally inactive on H3 receptor^[1].
In Vivo:AVN-101 (0.05 mg/kg; i.p.; once daily; for 4 days) hydrochloride reduces immobility in the forced swim test in mice^[1].
AVN-101 (0.02-5 mg/kg; i.p.; once) hydrochloride prevents Scopolamine (HY-N0296)-induced amnesia in a passive avoidance test in mice when administered at a dose of 0.05 mg/kg^[1].
AVN-101 (0.2, 1, and 5 mg/kg) hydrochloride increases the time spent in the open arms of the elevated plus maze in mice^[1].
AVN-101 hydrochloride is poorly stable in murine plasma: by the end of 30-min incubation at room temperature, the residual amount of the original compound is reduced to 16%. At the same time, AVN-101 hydrochloride shows better stability in plasma samples taken from monkey and human: by the end of the 30-min incubation at room temperature, the residual amount of the original compound is reduced to only 45% and 68%, respectively^[1].