Related Experiment Video
Updated: Feb 17, 2026

Cheek Injection Model for Simultaneous Measurement of Pain and Itch-related Behaviors
Published on: September 27, 2019
Identification of potent lysophosphatidic acid receptor 5 (LPA5) antagonists as potential analgesic agents
Yuichiro Kawamoto1, Ryushi Seo1, Nobuhito Murai1
1Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.
Abstract:
Lysophosphatidic acid (LPA) plays an important role in a variety of cellular functions. In particular, LPA5 receptor is highly expressed in spinal cord and dorsal root ganglion, which are associated with pain. This fact prompted us to hypothesize that LPA5 antagonists show analgesic effects. To search for potent LPA5 antagonists with blood brain barrier (BBB) permeability, we conducted high throughput screening (HTS). In HTS campaign, we found a 2H-isoquinoline-1-one scaffold showing antagonistic activity against LPA5 and synthesized a series of 2H-isoquinoline-1-one derivatives and evaluated their LPA5 activities. Among these compounds, compound 7e showed potent LPA5 activity with an IC50 value of 0.12 μM, and acceptable BBB permeability. Furthermore, it showed effective analgesic effect in a chronic constriction injury rat model. Therefore, 7e may have a potential as novel pain therapeutic approach.
More Related Videos
06:54Author Spotlight: Enhanced Method for Evaluating Analgesic Effects — Dual Hind Paw Carrageenan Injection in Mice
Published on: November 15, 2024
09:39Establishing a Mouse Model of a Pure Small Fiber Neuropathy with the Ultrapotent Agonist of Transient Receptor Potential Vanilloid Type 1
Published on: February 13, 2018
Related Concept Videos
Analgesia and Pain Management
Opioid Analgesics: Synthetic and Semisynthetic Opioids
Local Anesthetics: Mechanism of Action
Local anesthetics are amphiphilic molecules consisting of a hydrophobic aromatic part linked to a hydrophilic group by an ester or amide linkage. They are weak bases and are usually available as salts, which increases their solubility and stability. Once administered, LAs exist in the body either...
Opioid Receptors: Overview
Local Anesthetics: Chemistry and Structure-Activity Relationship
Local Anesthetics: Differential Sensitivity of Nerve Fibers