Fentanyl Analogs Exert Antinociceptive Effects via Sodium Channel Blockade in Mice.

IF 1.7 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Satoka Kasai, Natsuki Ogawa, Miho Takagi, Yukino Takahashi, Kosho Makino, Hironobu Arita, Hideyo Takahashi, Kazumi Yoshizawa
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Abstract

The formalin test is one approach to studying acute pain in rodents. Similar to formalin, injection with glutamate and veratrine can also produce a nociceptive response. This study investigated whether opioid-related compounds could suppress glutamate- and veratrine-induced nociceptive responses in mice at the same dose. The administration of morphine (3 mg/kg), hydromorphone (0.4 mg/kg), or fentanyl (0.03 mg/kg) suppressed glutamate-induced nociceptive response, but not veratrine-induced nociceptive response at the same doses. However, high doses of morphine (10 mg/kg), hydromorphone (2 mg/kg), or fentanyl (0.1 mg/kg) produced a significant reduction in the veratrine-induced nociceptive response. These results indicate that high doses are required when using morphine, hydromorphone, or fentanyl for sodium channel-related neuropathic pain, such as ectopic activity. As a result, concerns have arisen about overdose and abuse if the dose of opioids is steadily increased to relieve pain. In contrast, trimebutine (100 mg/kg) and fentanyl analog isobutyrylfentanyl (iBF; 0.1 mg/kg) suppressed both glutamate- and veratrine-induced nociceptive response. Furthermore, nor-isobutyrylfentanyl (nor-iBF; 1 mg/kg), which is a metabolite of iBF, suppressed veratrine-induced nociceptive response. Besides, the optimal antinociceptive dose of iBF, unlike fentanyl, only slightly increased locomotor activity and did not slow gastrointestinal transit. Cancer pain is a complex condition driven by inflammatory, neuropathic, and cancer-specific mechanisms. Thus, iBF may have the potential to be a superior analgesic than fentanyl.
芬太尼类似物通过阻断钠通道对小鼠产生抗痛觉作用
福尔马林试验是研究啮齿动物急性疼痛的一种方法。与福尔马林类似,注射谷氨酸和维拉汀也会产生痛觉反应。本研究调查了阿片类相关化合物是否能以相同剂量抑制谷氨酸钠和藜芦碱引起的小鼠痛觉反应。给小鼠注射吗啡(3 毫克/千克)、氢吗啡酮(0.4 毫克/千克)或芬太尼(0.03 毫克/千克)可抑制谷氨酸诱导的痛觉反应,但在相同剂量下不能抑制维拉汀诱导的痛觉反应。然而,大剂量吗啡(10 毫克/千克)、氢吗啡酮(2 毫克/千克)或芬太尼(0.1 毫克/千克)可显著降低维拉汀诱导的痛觉反应。这些结果表明,在使用吗啡、氢吗啡酮或芬太尼治疗钠通道相关的神经病理性疼痛(如异位活动)时,需要使用大剂量吗啡、氢吗啡酮或芬太尼。因此,如果为了缓解疼痛而不断增加阿片类药物的剂量,就会出现药物过量和滥用的问题。相比之下,曲美布汀(100 毫克/千克)和芬太尼类似物异丁酰芬太尼(iBF;0.1 毫克/千克)可抑制谷氨酸和维拉汀诱导的痛觉反应。此外,iBF 的代谢产物--nor-isobutylfentanyl(nor-iBF;1 毫克/千克)也能抑制维拉汀诱导的痛觉反应。此外,最佳抗痛剂量的 iBF 与芬太尼不同,只会轻微增加运动活动,不会减慢胃肠道转运。癌痛是一种由炎症、神经病理性和癌症特异性机制驱动的复杂病症。因此,iBF 有可能成为比芬太尼更好的镇痛药。
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来源期刊
CiteScore
3.50
自引率
5.00%
发文量
247
审稿时长
2 months
期刊介绍: Biological and Pharmaceutical Bulletin (Biol. Pharm. Bull.) began publication in 1978 as the Journal of Pharmacobio-Dynamics. It covers various biological topics in the pharmaceutical and health sciences. A fourth Society journal, the Journal of Health Science, was merged with Biol. Pharm. Bull. in 2012. The main aim of the Society’s journals is to advance the pharmaceutical sciences with research reports, information exchange, and high-quality discussion. The average review time for articles submitted to the journals is around one month for first decision. The complete texts of all of the Society’s journals can be freely accessed through J-STAGE. The Society’s editorial committee hopes that the content of its journals will be useful to your research, and also invites you to submit your own work to the journals.
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