NR2B-selective conantokin peptide inhibitors of the NMDA receptor display enhanced antinociceptive properties compared to non-selective conantokins

摘要: Abstract NR2B-selective inhibitors show lower side-effects in preclinical pain models than non-selective NMDA receptor (NMDAR) antagonists, but it is unclear whether the improved safety of due to their subtype selectivity or a unique mode inhibition receptor. In this study, analgesic effects intracerebral bolus injections conantokin peptides with different NMDAR subunit were determined mice by standard hot-plate test, and following stimuli acetic acid, formalin complete Freund’s adjuvant (CFA). model, con-G[S16Y], inhibitor, showed highest activity among tested. acid- CFA-induced models, con-G[S16Y] and, lesser extent, con-G exhibited higher compared inhibitors, such as con-R[1–17]. while all could partially suppress first phase response, only significantly inhibited second response suppressed paw edema. Our results suggest that antinociceptive action conantokins may be related NR2B-selectivity these useful both neurobiological tools for probing mechanisms nociception therapeutic agents relief.