title: Adenine-based acyclic nucleotides as novel P2X3 receptor ligands.
abstract: A new series of acyclic nucleotides based on the adenine skeleton and bearing in 9-position a phosphorylated four carbon chain has been synthesized. Various substituents were introduced in 2-position of the adenine core. The new compounds were evaluated on rat P2X3 receptors, using patch clamp recording from HEK transfected cells and the full P2X3 agonist alpha,beta-meATP as reference compound. The results suggest that certain acyclic nucleotides, in particular compounds 28 and 29, are endowed with modest partial agonism on P2X3 receptors. This is an interesting property that can depress the function of P2X3 receptors, whose activation is believed to be involved in a number of chronic pain conditions including neuropathic pain and migraine. In fact, the new acyclic nucleotides are able to persistently block (by desensitization) P2X3 receptor activity after a brief, modest activation, yet leaving the ability of sensory neurons to mediate responses to standard painful stimuli via a lower level of signaling.
authors.affiliation: Department of Chemical Sciences, University of Camerino, Via S. Agostino 1, 62032 Camerino, Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Volpini
authors.forename: Ram Chandra
authors.initials: RC
authors.lastname: Mishra
authors.forename: Dhuldeo D
authors.initials: DD
authors.lastname: Kachare
authors.forename: Diego
authors.initials: D
authors.lastname: Dal Ben
authors.forename: Catia
authors.initials: C
authors.lastname: Lambertucci
authors.forename: Ippolito
authors.initials: I
authors.lastname: Antonini
authors.forename: Sauro
authors.initials: S
authors.lastname: Vittori
authors.forename: Gabriella
authors.initials: G
authors.lastname: Marucci
authors.forename: Elena
authors.initials: E
authors.lastname: Sokolova
authors.forename: Andrea
authors.initials: A
authors.lastname: Nistri
authors.forename: Gloria
authors.initials: G
authors.lastname: Cristalli
mesh_terms: D000227:Adenine Nucleotides / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D058910:Purinergic P2 Receptor Agonists; D051381:Rats; D058477:Receptors, Purinergic P2X3; D013329:Structure-Activity Relationship
chemical_list: D000227:Adenine Nucleotides; D008024:Ligands; C546407:P2RX3 protein, human; C546410:P2rx3 protein, rat; D058910:Purinergic P2 Receptor Agonists; D058477:Receptors, Purinergic P2X3