I am a
Home I AM A Search Login

Papers of the Week

Papers: 5 Nov 2022 - 11 Nov 2022

Pharmacology/Drug Development

2022 Oct 31

Life Sci

Extracellular binding sites of positive and negative allosteric P2X4 receptor modulators.


Weinhausen S, Nagel J, Namasivayam V, Spanier C, Abdelrahman A, Hanck T, Hausmann R, Müller CE
Life Sci. 2022 Oct 31:121143.
PMID: 36328074.


P2X receptors are ATP-gated ion channels which play a role in many pathophysiological conditions. They are considered as novel drug targets, particularly in the fields of pain, (neuro) inflammation, and cancer. Due to difficulties in developing drug-like orthosteric ligands that bind to the highly polar ATP binding site, the design of positive and negative allosteric modulators (PAMs and NAMs) is a promising strategy. The P2X4 receptor was proposed as a novel target for neuropathic and inflammatory pain (antagonists), and for the treatment of alcoholism (PAMs). So far, little is known about the allosteric binding site(s) of P2X4 receptors. The aim of this study is to identify the binding site (s) of the macrocyclic natural product ivermectin, the urea derivative BX430, and the antidepressant drug paroxetine that act as allosteric modulators of P2X4 receptors.