Reversal of oxycodone and hydrocodone tolerance by diazepam.
Reversal of oxycodone and hydrocodone tolerance by diazepam.
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DOI：
10.1016/j.brainres.2017.08.017
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发表时间：
2017-11-01
期刊：
影响因子：
2.9
通讯作者：
Dewey WL
中科院分区：
文献类型：
--
作者：
Gonek M;Akbarali HI;Henderson G;Dewey WL
疾病控制中心宣布阿片类药物滥用是一种流行病。过量死亡在很大程度上被认为是阿片类药物过量消费的结果。然而，在许多这些情况下，类阿片滥用者往往是多种药物滥用者。苯二氮卓类药物是最常见的共同滥用物质之一，对阿片类药物使用者构成重大风险。2016年，FDA要求对处方阿片类镇痛药和苯二氮卓类药物同时使用这些药物的严重风险进行黑框警告-FDA最强烈的警告。我们研究的重点是评估这两类药物之间的相互作用。我们调查了地西泮是否增加了阿片类药物的耐受性，或者它们是否改变了阿片类药物的耐受性水平。在本研究中，我们发现，抗伤害耐受性，开发到羟考酮重复给药逆转了急性剂量的地西泮。对氢可酮的镇痛耐受性也可通过急性注射地西泮逆转;然而，与逆转羟考酮诱导的耐受性相比，需要高4倍的地西泮剂量。这些剂量的地西泮不会增强任何阿片类药物的急性抗伤害作用。逆转羟考酮抗伤害性耐受的相同剂量的地西泮也逆转羟考酮运动耐受，但没有增强作用。这些研究表明，地西泮不会增强处方阿片类药物的急性效应，但会逆转长期给药后产生的耐受性。
The Centers for Disease Control has declared opioid abuse to be an epidemic. Overdose deaths are largely assumed to be the result of excessive opioid consumption. In many of these cases, however, opioid abusers are often polydrug abusers. Benzodiazepines are one of the most commonly co-abused substances and pose a significant risk to opioid users. In 2016, the FDA required boxed warnings – the FDA’s strongest warning – for prescription opioid analgesics and benzodiazepines about the serious risks associated with using these medications at the same time. The point of our studies was to evaluate the interactions between these two classes of drugs. We investigated whether diazepam adds to the depressant effects of opioids or do they alter the levels of tolerance to opioids. In the present study, we have found that the antinociceptive tolerance that developed to repeated administration of oxycodone was reversed by an acute dose of diazepam. Antinociceptive tolerance to hydrocodone was also reversed by acute injection of diazepam; however, a four-fold higher dose of diazepam was required when compared to reversal of oxycodone-induced tolerance. These doses of diazepam did not potentiate the acute antinociceptive effect of either opioid. The same dose of diazepam that reversed oxycodone antinociceptive tolerance also reversed oxycodone locomotor tolerance while having no potentiating effects. These studies show that diazepam does not potentiate the acute effect of prescription opioids but reverses the tolerance developed after chronic administration of the drugs.
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DOI：
10.1038/npp.2015.201
发表时间：
2016-02
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
Hill R;Lyndon A;Withey S;Roberts J;Kershaw Y;MacLachlan J;Lingford-Hughes A;Kelly E;Bailey C;Hickman M;Henderson G
通讯作者：
Henderson G
DOI：
10.1124/jpet.109.161455
发表时间：
2010-03-01
影响因子：
3.5
作者：
Hull, L. C.;Llorente, J.;Dewey, W. L.
通讯作者：
Dewey, W. L.
影响因子：
3.6
作者：
JOHNSON, DW;GLICK, SD
通讯作者：
GLICK, SD
DOI：
10.1016/0306-3623(92)90158-g
发表时间：
1992-07-01
期刊：
GENERAL PHARMACOLOGY
影响因子：
--
作者：
SIERRALTA, F;MIRANDA, HF
通讯作者：
MIRANDA, HF
影响因子：
4.2
作者：
Zacny, James R.;Gutierrez, Sandra
通讯作者：
Gutierrez, Sandra