科研之友
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摘要
The present study was designed to investigate the antinociception of spirocyclopiperazinium salt compound LXM-10-M (2,4-dimethyl-9-beta m-hydroxyphenylethyl-3-oxo-6, 9-diazaspiro [5.5] undecane chloride) in thermal and chemical pain models, and further to explore the molecular target and potential signal pathway. We assessed the antinociception of LXM-10-M in hot-plate test, formalin test and acetic acid writhing test in mice. The possible changes of calcium/calmodulin-dependent protein kinase II alpha (CaMKII alpha)/cAMP response element-binding protein (CREB)/calcitonin gene related peptide (CGRP) signaling pathway were detected by Western Blot in mice. Administration of LXM-10-M produced significant antinociception in hot-plate test, formalin test and acetic acid writhing test in mice, with no obvious toxicity. The antinociceptive effects were blocked by pretreatment with methyllycaconitine citrate (MLA, alpha 7 nicotinic receptor antagonist) or tropicamide (TRO, M4 muscarinic receptor antagonist). Western blot analysis showed that the upregulations of p-CaMKII alpha, p-CREB and CGRP in the spinal cord were reduced by LXM-10-M in chemical pain model in mice, and the effects were blocked by MLA or TRO pretreatment. This is the first paper to report that LXM-10-M exerted significant antinociception, which may be attributed to the activation of alpha 7 nicotinic receptor and M4 muscarinic receptor and thereby triggering the inhibition of CaMKII alpha/CREB/CGRP signaling pathway in mice.
- 出版日期2016-1-5
- 单位北京大学
