Gonek Maciej, Akbarali Hamid I, Henderson Graeme, Dewey William L
Department of Pharmacology and Toxicology, Virginia Commonwealth University, 1112 East Clay Street, Richmond, VA 23298-0613, USA.
Department of Pharmacology and Toxicology, Virginia Commonwealth University, 1112 East Clay Street, Richmond, VA 23298-0613, USA.
Brain Res. 2017 Nov 1;1674:84-90. doi: 10.1016/j.brainres.2017.08.017. Epub 2017 Aug 19.
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 fourfold 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.
美国疾病控制中心已宣布阿片类药物滥用成为一种流行病。过量用药死亡大多被认为是阿片类药物过度消费的结果。然而，在许多此类案例中，阿片类药物滥用者往往同时滥用多种药物。苯二氮䓬类药物是最常被同时滥用的物质之一，对阿片类药物使用者构成重大风险。2016年，美国食品药品监督管理局（FDA）要求对处方阿片类镇痛药和苯二氮䓬类药物给出盒装警告——这是FDA最严厉的警告——以提示同时使用这些药物的严重风险。我们研究的目的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会增强阿片类药物的抑制作用，或者它们是否会改变对阿片类药物的耐受性水平。在本研究中，我们发现，急性给予一剂地西泮可逆转反复给予羟考酮所产生的抗伤害感受耐受性。急性注射地西泮也可逆转对氢可酮的抗伤害感受耐受性；然而，与逆转羟考酮诱导的耐受性相比，所需地西泮剂量要高四倍。这些地西泮剂量均未增强任何一种阿片类药物的急性抗伤害感受作用。逆转羟考酮抗伤害感受耐受性的相同剂量地西泮也逆转了羟考酮的运动耐受性，且无增强作用。这些研究表明，地西泮不会增强处方阿片类药物的急性作用，但可逆转长期用药后产生的耐受性。
