Rationale

Preclinical studies demonstrate that the NK1 receptor is involved in opioid reinforcement and withdrawal expression. Few studies have examined the impact of treatment with NK1 antagonists on opioid response in humans.

Objective

To explore the potential for a selective NK1 antagonist, tradipitant, to attenuate the abuse liability and reinforcing and analgesic effects of oxycodone in opioid-experienced individuals.

Methods

Participants with recreational opioid use, but without opioid physical dependence, were enrolled as inpatients for ~6 weeks (n = 8). A within-subject, double-blind, randomized, placebo-controlled, crossover design was employed. The pharmacodynamic response to intranasal oxycodone across a range of doses (0 to 30 mg) was examined during two counterbalanced maintenance periods (tradipitant 0 or 85 mg/bid). Oxycodone self-administration was assessed with a modified progressive ratio procedure, and analgesia was assessed with the cold pressor test.

Results

Oxycodone produced significant and dose-related increases on a broad array of prototypic opioid measures, including subjective ratings related to abuse liability (e.g., liking) and physiological outcomes (i.e., expired CO₂). Oxycodone self-administration increased with increasing dose, as did analgesia. Tradipitant largely did not alter any of these effects of oxycodone, with the exception of producing a reduction in ratings of desire for opioids.

Conclusions

Given that the vast majority of oxycodone effects were unchanged by tradipitant, these data do not provide support for the utility of NK1 antagonists as a potential treatment for opioid use disorder.

中文翻译：

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Tradipitant（一种选择性的NK1拮抗剂）对人体对羟考酮的反应的评估

基本原理

临床前研究表明，NK1受体参与阿片类药物的增强和戒断表达。很少有研究检查NK1拮抗剂治疗对人阿片样物质反应的影响。

客观的

探索潜在的选择性NK1拮抗剂tradipitant减轻阿片类药物治疗个体中羟考酮的滥用和镇痛作用。

方法

参加娱乐性阿片类药物治疗但无阿片类药物身体依赖性的参与者入院约6周（n  = 8）。采用受试者内部，双盲，随机，安慰剂对照，交叉设计。在两个维持平衡的时期（tradipitant 0或85 mg / bid），检查了在一系列剂量范围（0至30 mg）内对鼻内羟考酮的药效学反应。羟考酮的自我给药采用改良的渐进比例法进行评估，镇痛采用冷压试验进行评估。

结果

羟考酮对大量的阿片类药物原型措施产生了明显的剂量相关性增加，包括与滥用责任（例如，喜好）和生理结果（即，CO ₂过期）有关的主观评分。羟考酮的自我给药随着剂量的增加而增加，镇痛也是如此。除降低阿片类药物的需求量外，Tradipitant基本上不会改变羟考酮的任何这些作用。

结论

鉴于大多数羟考酮的作用在tradipitant中均未改变，所以这些数据不能为NK1拮抗剂作为阿片类药物使用障碍的潜在治疗方法提供支持。