In vivo and in vitro ADMET profiling and in vivo pharmacodynamic investigations of a selective alfa7 nicotinic acetylcholine receptor agonist with delta spirocyclic 2-isoxazoline molecular skeleton

(+/-)-3-Methoxy-1-oxa-2,7-diaza-7,10-ethanospiro[4.5] dec-2-ene sesquifumarate (+/-)-1 was previously characterized as the most selective agonist at alpha 7 neuronal nicotinic acetylcholine receptors in a series of spirocyclic quinuclidinyl-Delta(2)-isoxazoline derivatives. In this study, we performed different in vitro biological assays aimed at characterizing the ADMET properties of (+/-)-1. Then, we tested the compound in vivo in behavioral studies including classical novel object recognition and inhibitory avoidance tests in the rat, and a spatial memory assay in zebrafish involving a rapid T-maze task. The results indicated an overall favorable profile for (+/-)-1 in view of potential therapeutic applications targeting the central nervous system.