Add-on clinical effects of selective antagonist of 5HT6 receptors AVN-211 (CD-008-0173) in patients with schizophrenia stabilized on antipsychotic treatment: pilot study

Abstract

Selective 5HT6 antagonist AVN-211 (CD-008-0173) added antipsychotic and some procognitive (attention) effects to antipsychotic medication.

Arylpiperazinylalkyl derivatives of 8-amino-1,3-dimethylpurine-2,6-dione as novel multitarget 5-HT/D receptor agents with potential antipsychotic activity

“…Moreover, among the evaluated compounds, 43 and 46 showed 5-HT 6 antagonistic properties (IC 50 values ¼ 676 and 847 nM, respectively) ( Table 5). It seems important in terms of the recent reports that proposed 5-HT 6 receptor antagonists as potential drugs to treat cognitive impairments in schizophrenia 56,57 .…”

The selective 5-HT 6 receptor antagonist SLV has putative cognitive- and social interaction enhancing properties in rodent models of cognitive impairment

“…Avineuro Pharmaceuticals, Inc. reported positive results from a Phase IIa clinical proof of concept trial to assess the 5-HT 6 antagonist AVN-211 as an augmentation therapy to improve cognition in schizophrenia patients. In a double blind trial in 50 patients stabilized on an atypical antipsychotic therapy, AVN-211 (4 mg once a day) met the protocol criteria for positive results on the primary efficacy outcome measures (Morozova et al, 2014). Preclinical results with AVN-211 have been published this year (Ivachtchenko, Lavrovsky, & Ivanenkov, 2016).…”

Therapeutic Targeting of Autophagy

“…Consequently, several compounds including many that feed into mTOR signaling are moving forward towards clinical trials for different diseases (Table 1). One such class of drugs antagonize the G-protein coupled receptor, 5-HT 6 R, known to activate mTOR signaling in the brain (Meffre et al, 2012), and include the compounds AVN-211 (Ivachtchenko et al, 2016) (Morozova et al, 2014) (Phase IIa clinical trial for Schizophrenia, highlighting safety), Lu AE58054 (AKA idalopirdine)(Wilkinson et al, 2014)(Phase III clinical trial for AD - NCT02006641, NCT02006654, NCT02079246), and SB-742457(Maher-Edwards et al, 2010) (Phase II clinical trial for AD- NCT00224497, NCT0034819, NCT00708552, NCT00710684). …”