A novel lysophosphatidic acid receptor 1 antagonist with high brain penetrability has a curative effect in the empathic pain-related fibromyalgia model

  • J Pharmacol Sci. 2025 Jun;158(2):139-142. doi: 10.1016/j.jphs.2025.03.012.
Hiroyuki Neyama  1 ,  Naoki Dozono  2 ,  Yasuka Sahara  2 ,  Kenji Nishikawa  3 ,  Hiroshi Ueda  4
Affiliations
  • 1. Pharmacology and Therapeutic Innovation, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8521, Japan; Multiomics Platform, Center for Cancer Immunotherapy and Immunobiology, Kyoto University Graduate School of Medicine, Kyoto, 606-8507, Japan.
  • 2. Pharmacology and Therapeutic Innovation, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8521, Japan.
  • 3. Pharmaceutical Research Laboratory, Pharmaceutical Division, UBE Corporation, Yamaguchi, 755-8633, Japan.
  • 4. Pharmacology and Therapeutic Innovation, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8521, Japan; Graduate Institute of Pharmacology, National Defense Medical Center, Taiwan, 114201, Taipei, China; Laboratory for the Study of Pain, Research Institute for Production Development, Kyoto, 606-0805, Japan. Electronic address: [email protected].
PMID: 40288824 DOI: 10.1016/j.jphs.2025.03.012
Abstract

Lysophosphatidic acid receptor 1 (LPA1) plays a pivotal role in the pathophysiology of various diseases, especially chronic pain. In this study, we assessed the biochemical properties of Compound A, a novel LPA1 antagonist and its beneficial effects in the fibromyalgia (FM)-like pain model. Compound A was found to be a high-affinity and selective LPA1 antagonist and have high brain penetrability. Repeated oral administrations of Compound A reversed the hyperalgesia as late as 9 days after the treatments, suggesting this compound has a curative effect in the FM model.

Keywords
Antagonist; Fibromyalgia; Lysophosphatidic acid receptor 1.
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