ACS Chemical Neuroscience 

About: ACS Chemical Neuroscience is an academic journal published by American Chemical Society. The journal publishes majorly in the area(s): Medicine & Chemistry. It has an ISSN identifier of 1948-7193. Over the lifetime, 3469 publications have been published receiving 79432 citations. The journal is also known as: ACS Chem Neurosci & American Chemical Society chemical neuroscience.

Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host–Virus Interaction, and Proposed Neurotropic Mechanisms

Abstract: The recent outbreak of coronavirus infectious disease 2019 (COVID-19) has gripped the world with apprehension and has evoked a scare of epic proportion regarding its potential to spread and infect ...

Moving beyond Rules: The Development of a Central Nervous System Multiparameter Optimization (CNS MPO) Approach To Enable Alignment of Druglike Properties

Abstract: The interplay among commonly used physicochemical properties in drug design was examined and utilized to create a prospective design tool focused on the alignment of key druglike attributes. Using a set of six physicochemical parameters ((a) lipophilicity, calculated partition coefficient (ClogP); (b) calculated distribution coefficient at pH = 7.4 (ClogD); (c) molecular weight (MW); (d) topological polar surface area (TPSA); (e) number of hydrogen bond donors (HBD); (f) most basic center (pKa)), a druglikeness central nervous system multiparameter optimization (CNS MPO) algorithm was built and applied to a set of marketed CNS drugs (N = 119) and Pfizer CNS candidates (N = 108), as well as to a large diversity set of Pfizer proprietary compounds (N = 11 303). The novel CNS MPO algorithm showed that 74% of marketed CNS drugs displayed a high CNS MPO score (MPO desirability score ≥ 4, using a scale of 0−6), in comparison to 60% of the Pfizer CNS candidates. This analysis suggests that this algorithm could p...

A simple method for quantifying functional selectivity and agonist bias.

Abstract: Activation of seven-transmembrane (7TM) receptors by agonists does not always lead to uniform activation of all signaling pathways mediated by a given receptor. Relative to other ligands, many agonists are “biased” toward producing subsets of receptor behaviors. A hallmark of such “functional selectivity” is cell type dependence; this poses a particular problem for the profiling of agonists in whole cell test systems removed from the therapeutic one(s). Such response-specific cell-based variability makes it difficult to guide medicinal chemistry efforts aimed at identifying and optimizing therapeutically meaningful agonist bias. For this reason, we present a scale, based on the Black and Leff operational model, that contains the key elements required to describe 7TM agonism, namely, affinity (KA–1) for the receptor and efficacy (τ) in activating a particular signaling pathway. Utilizing a “transduction coefficient” term, log(τ/KA), this scale can statistically evaluate selective agonist effects in a manne...

Brain Tissue Responses to Neural Implants Impact Signal Sensitivity and Intervention Strategies

Abstract: Implantable biosensors are valuable scientific tools for basic neuroscience research and clinical applications. Neurotechnologies provide direct readouts of neurological signal and neurochemical processes. These tools are generally most valuable when performance capacities extend over months and years to facilitate the study of memory, plasticity, and behavior or to monitor patients’ conditions. These needs have generated a variety of device designs from microelectrodes for fast scan cyclic voltammetry (FSCV) and electrophysiology to microdialysis probes for sampling and detecting various neurochemicals. Regardless of the technology used, the breaching of the blood–brain barrier (BBB) to insert devices triggers a cascade of biochemical pathways resulting in complex molecular and cellular responses to implanted devices. Molecular and cellular changes in the microenvironment surrounding an implant include the introduction of mechanical strain, activation of glial cells, loss of perfusion, secondary metaboli...

Defining Desirable Central Nervous System Drug Space through the Alignment of Molecular Properties, in Vitro ADME, and Safety Attributes

Abstract: As part of our effort to increase survival of drug candidates and to move our medicinal chemistry design to higher probability space for success in the Neuroscience therapeutic area, we embarked on a detailed study of the property space for a collection of central nervous system (CNS) molecules. We carried out a thorough analysis of properties for 119 marketed CNS drugs and a set of 108 Pfizer CNS candidates. In particular, we focused on understanding the relationships between physicochemical properties, in vitro ADME (absorption, distribution, metabolism, and elimination) attributes, primary pharmacology binding efficiencies, and in vitro safety data for these two sets of compounds. This scholarship provides guidance for the design of CNS molecules in a property space with increased probability of success and may lead to the identification of druglike candidates with favorable safety profiles that can successfully test hypotheses in the clinic.