Reversal of morphine, methadone and heroin induced effects in mice by naloxone methiodide
Reversal of morphine, methadone and heroin induced effects in mice by naloxone methiodide
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DOI：
10.1016/j.lfs.2005.05.062
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发表时间：
2006-01-11
期刊：
影响因子：
6.1
通讯作者：
Irvine, RJ
中科院分区：
文献类型：
--
作者：
Lewanowitsch, T;Miller, JH;Irvine, RJ
阿片类药物过量通常与阿片类药物引起的呼吸抑制有关，是治疗性和非法使用阿片类药物的问题。虽然类阿片作用所涉及的中枢机制已得到充分描述，但也有人提出，外周成分可能有助于所观察到的作用。本研究旨在进一步验证外周作用的甲碘化纳洛酮对各种阿片受体激动剂产生的呼吸、镇痛和戒断作用的影响。在雄性Swiss-Albino小鼠中比较吗啡、美沙酮和海洛因的呼吸和镇痛作用，并确定每种阿片类药物的呼吸抑制ED 80剂量。这些剂量（吗啡9 mg/kg i. p.，美沙酮7 mg/kg i. p.，和海洛因17 mg/kg i. p.）用于显示纳洛酮（3 mg/kg i. p.）和纳洛酮甲碘化物（30-100 mg/kg i. p.）可以逆转这些阿片激动剂的呼吸和镇痛作用，但只有纳洛酮促使戒断。在雌性C57 BL/6 J小鼠中使用气压体积描记法进行的进一步研究发现，两种阿片类拮抗剂都可以逆转美沙酮诱导的呼吸频率降低和潮气量增加。其影响似乎不依赖于应变或性别。结论：甲碘纳洛酮可逆转多种阿片受体激动剂的呼吸和镇痛作用，而不诱导阿片戒断。(c)2005年爱思唯尔公司All rights reserved.
Opioid overdose, which is commonly associated with opioid induced respiratory depression, is a problem with both therapeutic and illicit opioid use. While the central mechanisms involved in the effects of opioids are well described, it has also been suggested that a peripheral component may contribute to the effects observed. This study aimed to further characterise the effects of the peripherally acting naloxone methiodide on the respiratory, analgesic and withdrawal effects produced by various opioid agonists. A comparison of the respiratory and analgesic effects of morphine, methadone and heroin in male Swiss-Albino mice was conducted and respiratory depressive ED80 doses of each opioid determined. These doses (morphine 9 mg/kg i.p., methadone 7 mg/kg i.p., and heroin 17 mg/kg i.p.) were then used to show that both naloxone (3 mg/kg i.p.) and naloxone methiodide (30-100 mg/kg i.p.) could reverse the respiratory and analgesic effects of these opioid agonists, but only naloxone precipitated withdrawal. Further investigation in female C57BL/6J mice using barometric plethysmography found that both opioid antagonists could reverse methadone induced decreases in respiratory rate and increases in tidal volume. Its effects do not appear to be strain or sex dependent. It was concluded that naloxone methiodide can reverse the respiratory and analgesic actions of a variety of opioid agonists, without inducing opioid withdrawal. (c) 2005 Elsevier Inc. All rights reserved.