RESUMO
Cannabidiol is the nonpsychoactive natural component of C. sativa that has been shown to be neuroprotective in multiple animal models. Our interest is to advance a therapeutic candidate for the orphan indication hepatic encephalopathy (HE). HE is a serious neurological disorder that occurs in patients with cirrhosis or liver failure. Although cannabidiol is effective in models of HE, it has limitations in terms of safety and oral bioavailability. Herein, we describe a series of side chain modified resorcinols that were designed for greater hydrophilicity and "drug likeness", while varying hydrogen bond donors, acceptors, architecture, basicity, neutrality, acidity, and polar surface area within the pendent group. Our primary screen evaluated the ability of the test agents to prevent damage to hippocampal neurons induced by ammonium acetate and ethanol at clinically relevant concentrations. Notably, KLS-13019 was 50-fold more potent and >400-fold safer than cannabidiol and exhibited an in vitro profile consistent with improved oral bioavailability.
RESUMO
Optical imaging based on intrinsic signals is a powerful method to visualize the activities of neural assembly in the cortex of animals in vivo, especially the detailed functional architecture of the visual cortex. Here, a new index, two-dimensional (2D) C0 complexity has been used to give a quantitative measure of the spatial pattern of the neural activity in orientation maps optically recorded from the visual cortex of cats globally. Results show that 2D C0 complexity could be employed to reveal the dynamic process of generating an orientation map in the visual cortex, and describe the variance of the neural responses in cortical area 17 under high and normal intraocular pressure. This suggests that 2D C0 could be used as a new quantitative measure for analyzing the intrinsic signal optical images.