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Neuropathic pain (NP) is a complex chronic pain state with a prevalence of almost 10% in the general population. Pharmacological options for NP are limited and weakly effective, so there is a need to develop more efficacious NP attenuating drugs. Activation of the type 1 lysophosphatidic acid (LPA 1 ) receptor is a crucial factor in the initiation of NP. Hence, it is conceivable that a functional antagonism strategy could lead to NP mitigation. Here we describe a new series of LPA 1 agonists among which derivative ( S )- 17 (UCM-05194) stands out as the most potent and selective LPA 1 receptor agonist described so far ( E  max = 118%, EC 50 = 0.24 μM, K  D = 19.6 nM; inactive at autotaxin and LPA 2-6 receptors). This compound induces characteristic LPA 1 -mediated cellular effects and prompts the internalization of the receptor leading to its functional inactivation in primary sensory neurons and to an efficacious attenuation of the pain perception in an in vivo model of NP.

A Novel Agonist of the Type 1 Lysophosphatidic Acid Receptor (LPA1), UCM-05194, Shows Efficacy in Neuropathic Pain Amelioration

A Novel Agonist of the Type 1 Lysophosphatidic Acid Receptor (LPA₁), UCM-05194, Shows Efficacy in Neuropathic Pain Amelioration