%0 Journal Article
%A González Gil, Inés
%A Zian, Debora
%A Vázquez Villa, María Del Henar
%A Hernández Torres, Gloria
%A Martínez, R. Fernando
%A Khiar Fernández, Nora
%A Rivera, Richard
%A Kihara, Yasuyuki
%A Devesa, Isabel
%A Mathivanan, Sakthikumar
%A Rosell del Valle, Cristina
%A Zambrana Infantes, Emma
%A Puigdomenech, María
%A Cincilla, Giovanni
%A Sánchez Martínez, Melchor
%A Rodríguez De Fonseca, Fernando Antonio
%A Ferrer Montiel, Antonio V.
%A Chun, Jerold
%A López Vales, Ruben
%A López Rodríguez, María Luz
%A Ortega Gutiérrez, Silvia
%T A Novel Agonist of the Type 1 Lysophosphatidic Acid Receptor (LPA1), UCM-05194, Shows Efficacy in Neuropathic Pain Amelioration
%D 2019
%U https://hdl.handle.net/20.500.14352/103163
%X ABSTRACT: Neuropathic pain (NP) is a complex chronicpain state with a prevalence of almost 10% in the generalpopulation. Pharmacological options for NP are limited andweakly effective, so there is a need to develop more efficaciousNP attenuating drugs. Activation of the type 1 lysophosphatidic acid (LPA1) receptor is a crucial factor in the initiation ofNP. Hence, it is conceivable that a functional antagonismstrategy could lead to NP mitigation. Here we describe a newseries of LPA1 agonists among which derivative (S)-17(UCM-05194) stands out as the most potent and selectiveLPA1 receptor agonist described so far (Emax = 118%, EC50 =0.24 μM, KD = 19.6 nM; inactive at autotaxin and LPA2−6 receptors). This compound induces characteristic LPA1-mediatedcellular effects and prompts the internalization of the receptor leading to its functional inactivation in primary sensory neuronsand to an efficacious attenuation of the pain perception in an in vivo model of NP.
%~