RT Journal Article
T1 β–Lactam TRPM8 Antagonist RGM8-51 Displays Antinociceptive Activity in Different Animal Models
A1 Martín Escura, Cristina
A1 Medina Peris, Alicia
A1 Spear, Luke A.
A1 de la Torre Martínez, Roberto
A1 Olivos Ore, Luis Alcides
A1 Barahona Gomáriz, María Victoria
A1 González Rodríguez de Castro, Sara
A1 Fernández Ballester, Gregorio
A1 Fernández Carvajal, Asia
A1 Rodríguez Artalejo, Antonio
A1 Ferrer Montiel, Antonio
A1 González Muñiz, Rosario
AB Transient receptor potential melastatin subtype 8 (TRPM8) is a cation channel extensively expressed in sensory neurons and implicated in different painful states. However, the effectiveness of TRPM8 modulators for pain relief is still a matter of discussion, since structurally diverse modulators lead to different results, depending on the animal pain model. In this work, we described the antinociceptive activity of a β–lactam derivative, RGM8-51, showing good TRPM8 antagonist activity, and selectivity against related thermoTRP channels and other pain-mediating receptors. In primary cultures of rat dorsal root ganglion (DRG) neurons, RGM8-51 potently reduced menthol-evoked neuronal firing without affecting the major ion conductances responsible for action potential generation. This compound has in vivo antinociceptive activity in response to cold, in a mouse model of oxaliplatin-induced peripheral neuropathy. In addition, it reduces cold, mechanical and heat hypersensitivity in a rat model of neuropathic pain arising after chronic constriction of the sciatic nerve. Furthermore, RGM8-51 exhibits mechanical hypersensitivity-relieving activity, in a mouse model of NTG-induced hyperesthesia. Taken together, these preclinical results substantiate that this TRPM8 antagonist is a promising pharmacological tool to study TRPM8-related diseases.
PB MPDI
SN 1422-0067
YR 2022
FD 2022-02-28
LK https://hdl.handle.net/20.500.14352/72502
UL https://hdl.handle.net/20.500.14352/72502
LA eng
NO Ministerio de Ciencia e Innovación (MICINN)/FEDER
NO Comunidad de Madrid
NO Consejo Superior de Investigaciones Científicas (CSIC)
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 27 abr 2025