更新于：2024-12-11

Oxycodone

羟考酮

更新于：2024-12-11

概要

概要

基本信息

简介Oxycodone是一种阿片类止痛药物，有时也被称为麻醉剂。它是一种通过结合大脑和脊髓中的μ、κ和δ受体来缓解疼痛的阿片类药物。Oxycodone的化学名称为4,5 α-环氧-14-羟基-3-甲氧基-17-甲基吗啡酮-6-酮。该药物在美国和中国获得批准，并由Collegium制药公司生产。Oxycodone是一种高效的止痛药物，常用于管理中度到重度疼痛，如癌症、手术或创伤引起的疼痛。然而，由于其成瘾和滥用的潜在风险，它被列为受控物质，只能在医疗专业人士的指导下使用。

药物类型

小分子化药

别名

(-)-14-Hydroxydihydrocodeinone、4,5-Epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one、4,5alpha-Epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one

+ [21]

靶点

Opioid receptors

作用机制

Opioid receptors激动剂(阿片样受体激动剂)

治疗领域

神经系统疾病其他疾病

在研适应症

疼痛术后疼痛急性疼痛+ [1]

非在研适应症

癌症疼痛慢性疼痛腰痛+ [3]

原研机构

Collegium Pharmaceutical, Inc.

在研机构

Ensysce Biosciences, Inc.Napp Pharmaceutical Holdings Ltd.

Collegium Pharmaceutical, Inc.

非在研机构

Mundipharma Research GmbH & Co. KG

萌蒂（中国）制药有限公司Grunenthal SA

最高研发阶段批准上市

首次获批日期

中国 (2004-01-21),

疼痛

最高研发阶段(中国)批准上市

特殊审评突破性疗法 (美国)、快速通道 (美国)

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结构

分子式C18H21NO4

InChIKeyBRUQQQPBMZOVGD-XFKAJCMBSA-N

CAS号76-42-6

关联

434

项与羟考酮相关的临床试验

NCT06602271 / Not yet recruiting临床3期

A Multicenter, Randomized, Double-Blind, Placebo- and Active-Controlled Study to Evaluate the Efficacy and Safety of PF614 for the Treatment of Moderate to Severe Pain After Abdominoplasty

The goal of this clinical trial is to evaluate the analgesic activity of PF614 (an oral oxycodone prodrug extended-release analgesic) for control of postsurgical pain in subjects scheduled for abdominoplasty surgery. The main question to be answered is:
• To assess the analgesic efficacy of PF614 compared to oxycodone hydrochloride (an immediate-release opioid analgesic) and placebo in subjects with moderate to severe pain following abdominoplasty Participants will be asked to take oral blinded doses of study medication at about one hour before surgery starts, and then every 6 hours after surgery for up to 4 days.
Participants will be asked to:
* Rate their pain on a 0-10 numerical rating scale (NRS) at various timepoints up to 5 days following surgery;
* Tell us about the need for rescue medication if they continue to have moderate-to-severe pain;
* Tell us about any side effects or adverse effects that they may experience to help us understand the safety and tolerability of the test medications;
* Provide periodic blood samples to help us understand how much study drug is in their system.
Participants will stay in a clinic setting and be monitored for safety for 5 days following surgery. We anticipate that participants will be discharged on Day 5, pending medical review, and then keep a diary to record study-related pain and adverse effects for an additional 2-4 days after discharge.

开始日期2025-03-01

申办/合作机构

Ensysce Biosciences, Inc.

NCT06721988 / Not yet recruitingN/AIIT

Exploring the Effect of Preventive Analgesia with Oxycodone and Parecoxib Sodium on the Chronification of Acute Pain in Adult Patients Underwent Laparoscopic-assisted Abdominal Major Surgery

The goal of this clinical trial is to learn if the administration of oxycodone for preventive analgesia works to reduce the chronification of acute postoperative pain in adult participants undergoing major abdominal surgery. The main question it aims to answer is:
• Does administration of oxycodone before surgical incision reduce the occurrence of chronic pain or relieve the chronic pain symptoms 3 months after the operation? Researchers will compare oxycodone + parecoxib sodium to placebo + parecoxib sodium combinations to see if oxycodone works to reduce the chronification of acute postoperative pain.
Participants will:
* Take oxycodone + parecoxib sodium or placebo + parecoxib sodium combinations before the surgical incision
* Cooperate with the follow-up staffs and complete some checkups or tests within 3 months after the operation.

开始日期2025-01-01

申办/合作机构

华中科技大学同济医学院附属同济医院

[+2]

NCT06505187 / Recruiting临床2期

Celecoxib Pain Management Following Superficial Parotidectomy: Opioid Sparing Protocol

The goal of this clinical trial is to find out whether pain can be managed after an operation with celecoxib instead of oxycodone. The main question it aims to answer is if use of celecoxib plus Tylenol reduces the need for oxycodone.
Researchers will compare the combination of celecoxib and Tylenol to a placebo to find out whether celecoxib works to manage pain.
Participants will:
* Take celecoxib, or a placebo, plus Tylenol with opioids as needed
* Keep a diary of their pain between visits
* Complete questionnaires

开始日期2024-12-01

申办/合作机构

University of Wisconsin Madison

100 项与羟考酮相关的临床结果

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100 项与羟考酮相关的转化医学

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100 项与羟考酮相关的专利（医药）

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4,910

项与羟考酮相关的文献（医药）

2025-02-01·BIOMATERIALS

The immunological and pharmacokinetic evaluation of Lipid-PLGA hybrid nanoparticle-based oxycodone vaccines

Article

作者: Pravetoni, Marco ; Hamid, Fatima A ; Rostamizadeh, Kobra ; Walter, Debra L. ; Runyon, Scott ; Vigliaturo, Jennifer R ; Zhang, Chenming ; Vigliaturo, Jennifer R. ; DeHority, Riley ; Hamid, Fatima A. ; Bian, Yuanzhi ; Hu, He ; Ehrich, Marion ; Walter, Debra L

The current opioid epidemic is one of the most profound public health crises facing the United States. Despite that it has been under the spotlight for years, available treatments for opioid use disorder (OUD) and overdose are limited to opioid receptor ligands such as the agonist methadone and the overdose reversing drugs such as naloxone. Vaccines are emerging as an alternative strategy to combat OUD and prevent relapse and overdose. Most vaccine candidates consist of a conjugate structure containing the target opioid attached to an immunogenic carrier protein. However, conjugate vaccines have demonstrated some intrinsic shortfalls, such as fast degradation and poor recognition by immune cells. To overcome these challenges, we proposed a lipid-PLGA hybrid nanoparticle (hNP)-based vaccine against oxycodone (OXY), which is one of the most frequently misused opioid analgesics. The hNP-based OXY vaccine exhibited superior immunogenicity and pharmacokinetic efficacy in comparison to its conjugate vaccine counterpart. Specifically, the hNP-based OXY vaccine formulated with subunit keyhole limpet hemocyanin (sKLH) as the carrier protein and aluminum hydroxide (Alum) as the adjuvant (OXY-sKLH-hNP(Alum)) elicited the most potent OXY-specific antibody response in mice. The induced antibodies efficiently bound with OXY molecules in blood and suppressed their entry into the brain. In a following dose-response study, OXY-sKLH-hNP(Alum) equivalent to 60 μg of sKLH was determined to be the most promising OXY vaccine candidate moving forward. This study provides evidence that hybrid nanoparticle-based vaccines may be superior vaccine candidates than conjugate vaccines and will be beneficial in treating those suffering from OUD.

2025-02-01·BIOCHEMICAL PHARMACOLOGY

Positive allosteric modulation of µ-opioid receptor – A new possible approach in the pain management?

Review

作者: Król, Wojciech ; Machelak, Weronika ; Zielińska, Marta

The antinociceptive effect of the opioid drugs is achieved through activation of the µ-opioid receptor (MOP). The orthosteric and allosteric sites of opioid receptors may be modulated, orthosteric site by endogenous i.e.β-endorphin and exogenous opioids (morphine, oxycodone, fentanyl); whereas BMS-986121, BMS-986122, Comp5, MS1, Ignavine or even oxytocin act on the allosteric site of the MOP. Opioid therapy is associated with numerous side effects, such as: respiratory depression, sedation, constipation, and importantly, prolonged therapy can influence the development of tolerance, overdose, and addiction. Opioid tolerance is a result of MOP internalization and desensitization, preceded by MOP phosphorylation, performed by protein kinases such as: PKA, PKC, GRKs or CaMKII. In vitro and in vivo data suggest that positive allosteric modulators may enhance antinociception triggered by orthosteric ligands and reduce side effects, which would allow the dose of opioids to be reduced and thus provide a more effective therapy. In this review, we present that positive modulation of the allosteric sites of MOP may constitute a new strategy for pain therapy.

2025-01-01·CLINICA CHIMICA ACTA

Direct analysis in real time mass spectrometry (DART-MS/MS) for rapid urine opioid detection in a clinical setting

Article

作者: El-Khoury, Joe M ; Tran, Minh Nguyet ; Cassella-McLane, Gina ; Shang, Emily ; Choucair, Ibrahim

BACKGROUND AND AIMS:

Current laboratory methods for opioid detection involve an initial screening with immunoassays which offers efficient but non-specific results and a subsequent liquid chromatography-tandem mass spectrometry (LC-MS/MS) confirmation which offers accurate results but requires extensive sample preparation and turnaround time. Direct Analysis in Real Time (DART) tandem mass spectrometry is evaluated as an alternative approach for accurate opioid detection with efficient sample preparation and turnaround time.

MATERIALS AND METHODS:

DART-MS/MS was optimized by testing the method with varying temperatures, operation modes, extraction methods, hydrolysis times, and vortex times. The method was evaluated for 12 opioids by testing the analytical measurement range, percent carryover, precision studies, stability, and method-to-method comparison with LC-MS/MS.

RESULTS:

DART-MS/MS shows high sensitivity and specificity for the detection of 6-acetylmorphine, codeine, hydromorphone, oxymorphone, hydrocodone, naloxone, buprenorphine, norfentanyl, and fentanyl in urine samples. However, its performance was suboptimal for norbuprenorphine, morphine and oxycodone.

CONCLUSION:

In this proof-of-concept study, DART-MS/MS is evaluated for its rapid quantitative definitive testing of opioids drugs in urine. Further research is needed to expand its application to other areas of drug testing.

240

项与羟考酮相关的新闻（医药）

2024-12-10

·access wire

Ensysce Biosciences Announces Commercial Supplier for Breakthrough Overdose Protection Drug Product

~ Supply Chain Now Fully Secure for PF614-MPAR ~ SAN DIEGO, CA / ACCESSWIRE / December 10, 2024 / Ensysce Biosciences, Inc. (NASDAQ:ENSC) ("Ensysce" or "Company"), a clinical-stage pharmaceutical company developing innovative solutions for severe pain relief while reducing the potential for opioid abuse and overdose, today announced the receipt of commitment of future supply of GMP nafamostat, a critical component of PF614-MPAR. This agreement fully secures the supply chain and allows Ensysce to reference the nafamostat Drug Master File of Aurore Life Sciences, a renowned specialty drug manufacturer.Dr. Lynn Kirkpatrick commented, "We are pleased to have received this early interest and commitment from Aurore as nafamostat is a vital component of our overdose protection program PF614-MPAR. Having a secure supply of this drug substance will accelerate our finalizing the drug product for PF614-MPAR, which is rapidly moving through clinical development. Ensysce has initiated additional programs with nafamostat as a single agent for other indications which will also benefit from this commitment, so we welcome Aurore as a critical partner in our pipeline development."About Ensysce BiosciencesEnsysce Biosciences is a clinical-stage pharmaceutical company using its proprietary technology platforms to develop safer prescription drugs. Leveraging its Trypsin-Activated Abuse Protection (TAAPTM) and Multi-Pill Abuse Resistance (MPAR®) platforms, the Company is developing unique, tamper-proof treatment options for pain that minimize the risk of both drug abuse and overdose. Ensysce's products are anticipated to provide safer options to treat patients suffering from severe pain and assist in preventing deaths caused by medication abuse. The platforms are covered by an extensive worldwide intellectual property portfolio for a wide array of prescription drug compositions. For more information, please visit www.ensysce.com.About Aurore Life SciencesAurore Life Sciences, established in 2017, is a leading manufacturer of Active Pharmaceutical Ingredients (APIs) and intermediates, offering high-quality, affordable bulk drug solutions to over 55 countries worldwide. With a pure-play focus on APIs and intermediates, Aurore is a fully backward-integrated pharmaceutical company dedicated to delivering to all regulated markets globally.Forward-Looking StatementsStatements contained in this press release that are not purely historical may be deemed to be forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995 and other federal securities laws. Without limiting the foregoing, the use of words such as "may," "intends," "can," "might," "will," "expect," "plan," "possible," "believe" and other similar expressions are intended to identify forward-looking statements. The product candidates discussed are in clinic and not approved and there can be no assurance that the clinical programs will be successful in demonstrating safety and/or efficacy, that Ensysce will not encounter problems or delays in clinical development, or that any product candidate will ever receive regulatory approval or be successfully commercialized. All forward-looking statements are based on estimates and assumptions by Ensysce's management that, although Ensysce believes to be reasonable, are inherently uncertain. All forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those that Ensysce expected. In addition, Ensysce's business is subject to additional risks and uncertainties, including among others, the initiation and conduct of preclinical studies and clinical trials; the timing and availability of data from preclinical studies and clinical trials; expectations for regulatory submissions and approvals; potential safety concerns related to, or efficacy of, Ensysce's product candidates; the availability or commercial potential of product candidates; the ability of Ensysce to fund its continued operations, including its planned clinical trials; the dilutive effect of stock issuances from our fundraising; and Ensysce's and its partners' ability to perform under their license, collaboration and manufacturing arrangements. These statements are also subject to a number of material risks and uncertainties that are described in Ensysce's most recent quarterly report on Form 10-Q and current reports on Form 8-K, which are available, free of charge, at the SEC's website at www.sec.gov. Any forward-looking statement speaks only as of the date on which it was made. Ensysce undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required under applicable law.Ensysce Biosciences Company ContactLynn Kirkpatrick, Ph.D.Chief Executive Officer(858) 263-4196Ensysce Biosciences Investor Relations Contact:MZ Group North America Shannon Devine203-741-8811[email protected]SOURCE: Ensysce Biosciences Inc.

2024-12-04

·access wire

Ensysce Biosciences Announces Strategic Partnership for the Development and Commercial Launch of PF614 and PF614-MPAR

~ $10 Million Commitment from Specialty Drug Manufacturer to Support Commercialization Efforts ~ SAN DIEGO, CA / ACCESSWIRE / December 4, 2024 / Ensysce Biosciences, Inc. (NASDAQ:ENSC) ("Ensysce" or "Company"), a clinical-stage pharmaceutical company developing innovative solutions for severe pain relief while reducing the potential for opioid abuse and overdose, today announced the initiation of a strategic partnership with a leading specialty drug manufacturer for the development and commercial launch of PF614 and PF614-MPAR drug products.This collaboration underscores a shared commitment to achieving swift regulatory approval and efficient development of the Company's innovative drug products. The strategic partnership will provide Ensysce with the clinical trial material, drug products for regulatory submissions, and initial commercial batches of PF614 and PF614-MPAR. The partner's services will also encompass the complete manufacturing process, including packaging, labeling, and shipment of the products, ensuring a seamless transition from regulatory approval to market entry.As part of this partnership, the specialty drug manufacturer will take an equity position in Ensysce, facilitating resource allocation to clinical trials and commercialization activities. The agreement also secures key Chemistry Manufacturing and Control (CMC) elements of the New Drug Application (NDA) submission.Dr. Lynn Kirkpatrick, CEO of Ensysce Biosciences, stated, "This partnership strengthens our ability to deliver quality drug products for clinical and commercial purposes starting with PF614 and PF614-MPAR. It ensures that all aspects of manufacturing, packaging, and distribution are handled efficiently, enabling us to focus on helping patients suffering from severe pain with innovative and safer solutions."About Ensysce BiosciencesEnsysce Biosciences is a clinical-stage pharmaceutical company using its proprietary technology platforms to develop safer prescription drugs. Leveraging its Trypsin-Activated Abuse Protection (TAAP TM ) and Multi-Pill Abuse Resistance (MPAR®) platforms, the Company is developing unique, tamper-proof treatment options for pain that minimize the risk of both drug abuse and overdose. Ensysce's products are anticipated to provide safer options to treat patients suffering from severe pain and assist in preventing deaths caused by medication abuse. The platforms are covered by an extensive worldwide intellectual property portfolio for a wide array of prescription drug compositions. For more information, please visit www.ensysce.com.Forward-Looking StatementsStatements contained in this press release that are not purely historical may be deemed to be forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995 and other federal securities laws. Without limiting the foregoing, the use of words such as "may," "intends," "can," "might," "will," "expect," "plan," "possible," "believe" and other similar expressions are intended to identify forward-looking statements. The product candidates discussed are in clinic and not approved and there can be no assurance that the clinical programs will be successful in demonstrating safety and/or efficacy, that Ensysce will not encounter problems or delays in clinical development, or that any product candidate will ever receive regulatory approval or be successfully commercialized. All forward-looking statements are based on estimates and assumptions by Ensysce's management that, although Ensysce believes to be reasonable, are inherently uncertain. All forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those that Ensysce expected. In addition, Ensysce's business is subject to additional risks and uncertainties, including among others, the initiation and conduct of preclinical studies and clinical trials; the timing and availability of data from preclinical studies and clinical trials; expectations for regulatory submissions and approvals; potential safety concerns related to, or efficacy of, Ensysce's product candidates; the availability or commercial potential of product candidates; the ability of Ensysce to fund its continued operations, including its planned clinical trials; the dilutive effect of stock issuances from our fundraising; and Ensysce's and its partners' ability to perform under their license, collaboration and manufacturing arrangements. These statements are also subject to a number of material risks and uncertainties that are described in Ensysce's most recent quarterly report on Form 10-Q and current reports on Form 8-K, which are available, free of charge, at the SEC's website at www.sec.gov. Any forward-looking statement speaks only as of the date on which it was made. Ensysce undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required under applicable law.Ensysce Biosciences Company ContactLynn Kirkpatrick, Ph.D.Chief Executive Officer(858) 263-4196Ensysce Biosciences Investor Relations Contact:MZ Group North America Shannon Devine203-741-8811[email protected]SOURCE: Ensysce Biosciences Inc.

申请上市

2024-11-18

·CPHI制药在线

新型阿片类镇痛药物的研发进展

关注并星标CPHI制药在线阿片类镇痛药是目前已知疗效最好的镇痛药之一，然而其便秘、耐受和成瘾等毒副作用严重限制了其临床应用。近年来，随着对阿片受体信号转导机制的深入认知和药物设计技术的不断进步，研究者们尝试了许多有前景、不同于传统的改造吗啡骨架结构的全新方法，致力于开发低毒高效的阿片类镇痛药。 01 偏向型 μ 受体激动剂阿片类药物通过不同的细胞内信号途径产生不同的作用。研究发现，G蛋白偶联受体 (Gprotein-coupled receptor, GPCR)激活后，在其下游除了G蛋白依赖型通路外，还存在另一条由β-arrestin介导的信号通路，不同的配体可以不同程度地激活这两条通路，甚至只激活其中一条，这种现象称为“偏向性激活”。研究显示，G蛋白依赖型通路主要介导镇痛镇静，而β-arrestin 通路主要介导呼吸抑制、胃肠功能紊乱、药物耐受等。说明若某个阿片受体激动剂可以偏向性激动G蛋白信号通路，其镇痛疗效与毒副作用的平衡关系会更优，这为低毒高效阿片类镇痛新药的发现提供了理论基础。目前，丁丙诺啡、奥赛利定和PZM21 是比较有代表性的G蛋白偏向性激动剂。丁丙诺啡是由英国Reckitt Benckiser公司基于吗啡骨架所设计的，于 1978 年获批上市。该药不仅能够有效治疗急性和慢性疼痛，还可通过替代疗法减轻阿片类药物的成瘾性。丁丙诺啡的镇痛疗效媲美吗啡，但其呼吸抑制等不良反应的发生率较吗啡更低。奥赛利定，由美国 Trevena公司于2013 年研发。在细胞水平上，该药对G蛋白信号通路的激活能力与吗啡相近，但招募β-arrestin 2的能力远低于吗啡；在动物水平上，该药显示出略强于吗啡的镇痛效力，并且不易诱发呼吸抑制。2020年，奥赛利定获美国 FDA 批准上市，用于中重度急性疼痛的治疗，但该药仍会引发恶心、呕吐、便秘等不良反应。 PZM21是首个基于阿片受体晶体结构所设计的G蛋白偏向性激动剂。在细胞水平上，其偏向性与奥赛利定不相上下；在啮齿和灵长类动物水平上，其镇痛效力与吗啡、羟考酮相当且持续时间更久，并且没有成瘾性。但是，PZM21 仍未能避免便秘、耐药等不良反应。此外，引入苯并二氧戊环取代 PZM21 分子结构中的羟基，该衍生物可表现出比母体更强的镇痛活性和更大的G蛋白信号通路偏向性。有研究通过对配体-受体复合物冷冻电镜结构的解析和对比，发现 PZM21 和奥赛利定分别为完全不激活和部分激活 β-arrestin 信号通路，而芬太尼和吗啡则是强效激活β-arrestin 信号通路，这阐释了偏向性激动剂招募 β-arrestin 的结构细节，为开发低毒高效的偏向性阿片类镇痛药夯实了结构基础。近日，国内关于G蛋白偏向性阿片受体激动剂的临床研究取得重大突破。江苏恒瑞医药股份有限公司的泰吉利定（产品开发名为 SHR8554）是一种 μ 阿片受体的偏向性小分子激动剂，具有良好的镇痛作用、安全性和耐受性，于 2024 年 1 月 31 日获我国国家药品监督管理局批准上市，适用于腹部手术后的中重度疼痛，是国内首款自主研发的一类阿片类镇痛创新药。绿叶制药集团有限公司的G蛋白偏向性阿片受体激动剂 LPM-3480392 已先后在中国和美国完成了腹部手术中重度疼痛的Ⅱ期临床试验（CTR20222358、NCT06204120），关于骨科手术术后中重度疼痛的Ⅱ期临床试验（CTR20233389）正在有序开展中。 02 混合阿片受体激动剂以及 “一药多靶”策略多种药物联用的“鸡尾酒”疗法，在癌症、艾滋病和慢性疼痛等疾病治疗中均取得了良好成效。研发人员基于“鸡尾酒”疗法提出了“一药多靶”的多重药理学新理念，即作用于多个靶标的单一组分化合物，有助于平衡各靶标活性并产生协同作用。在痛觉相关的受体或信号通路中，μ阿片受体的调控效果最为显著。因此，阿片类“一药多靶”策略主要是围绕μ阿片受体开展的。根据靶标组合的不同，阿片类“一药多靶”药物主要分为下述两类。 ① 阿片受体家族不同亚型之间的组合，即：除靶向激动μ阿片受体以外，药物还作用于δ、κ 或 NOP 受体。研究发现，敲除 δ 受体可减轻 μ 受体激动剂的成瘾、耐受等副作用，以此为理论基础所设计的 μ 受体激动剂/δ 受体拮抗剂显示出更少的不良反应。有趣的是，μ/δ 受体双靶点激动剂同样显示出较好的镇痛潜力。此外，κ 和 NOP 受体也能够协同调节 μ 受体的生理效应。Cebranopadol 是一款极有代表性的“一药多靶”药物，由美国 Tris 公司开发。在细胞水平上，该药对多个阿片受体亚型都有较高的亲和力和激动活性（尤其是对μ和 NOP 受体），多靶点特性突出；在啮齿和灵长类动物水平上，该药的镇痛效力远高于吗啡，且不良反应更少。目前，该药在癌症疼痛、糖尿病周围神经病变、骨关节炎引发的慢性疼痛和药物滥用潜力评估等近10项临床试验中均取得了良好进展。 ② 阿片受体与非阿片受体的组合，除靶向激动μ阿片受体以外，药物还作用于非阿片系统的受体或信号通路，如神经肽FF（neuropeptide FF，NPFF）受体、神经激肽受体、胆囊收缩素受体等。以 NPFF 为例，有学者以阿片受体激动剂 morphiceptin 和 NPFF 类似物PFRTicNH2为母体设计了多靶点阿片肽药物 MCRT，该药显示出强效的镇痛活性和极少的不良反应；另有学者基于阿片受体激动剂和 NPFF 构建了 DN-9 等多个多靶点分子，其有效性和安全性均优于吗啡。在已上市的阿片类镇痛药中，具有“一药多靶”特性的药物占有很大比例，包括地佐辛和他喷他多等十余种药物都属于此类。相比吗啡等专一性 μ 阿片受体激动剂，多靶点阿片类镇痛药的安全性普遍较好。例如地佐辛，其呼吸抑制等不良反应的发生率非常低且有封顶效应，因而备受医患关注，占据了我国麻醉镇痛药市场约60% 的份额。多靶点药物的设计策略为安全高效的新型阿片类镇痛药的研发提供了更多可能性。 03 外周阿片受体激动剂众所周知，阿片受体在脑和脊髓之外的周围神经系统有着广泛的分布。透过血-脑屏障激活中枢神经系统的阿片受体，是阿片类药物发挥强效镇痛作用的关键，也是成瘾、过度镇静等副作用的根本原因。因此，“不上头”的外周阿片受体激动剂愈发受到关注。一种方法是研究本身不通过血脑屏障的药物，该研究集中于κ 受体激动剂，以asimadoline (EMD61753) 为代表，但 asimadoline 在镇痛方面表现差强人意，上市后主要用于肠易激综合征。再者，可采用纳米载体搭载阿片类药物，纳米载体无法通过血脑屏障，从而达到仅激动外周阿片受体的作用。法国学者开发出一种装载了亮氨酸脑啡肽 (leu-enkephalin, LENK) 的纳米药物，在动物模型中，该药成功的被血脑屏障阻隔，通过外周阿片受体实现炎症部位的长效止痛。另外，有学者设计出仅在特定 pH 环境中起作用的阿片受体激动剂，而炎性组织一般为酸性环境。该类药物以NFEPP 为代表，NFEPP 是基于芬太尼所设计的一种氟化衍生物。相比于芬太尼，该药不仅无法跨越血-脑屏障，氟原子的修饰作用还使其只有在酸性条件下才能与外周 μ 阿片受体结合，对呈现酸性微环境的病变组织实现靶向治疗。在结肠炎小鼠模型中，该药能够精准靶向炎症组织，有效缓解结肠疼痛，且完全不诱发成瘾、镇静、便秘等阿片样副作用。此外，研究人员基于 L-脑啡肽和角鲨烯的生物缀合物所开发的一种纳米载体镇痛药，通过制剂手段同样达到了不入脑而仅激活外周阿片受体的目的。 04 改变中枢分布动力学的阿片受体激动剂有假说认为 μ 受体激动剂的成瘾作用与其进入中枢的速度有关，但镇痛效果只与中枢暴露水平有关，那么开发以较低速率穿过血脑屏障的新型阿片受体激动剂，有可能降低成瘾。NKTR-181是一种聚合物-药物偶联物，通过聚乙二醇侧链 (polyethylene glycol, PEG) 来降低 μ 阿片类激动剂穿过血脑屏障的速度，在降低阿片类镇痛药成瘾性和滥用的同时，并具有显著的镇痛效力。目前，在腰痛和慢性非癌性痛病人中完成 3 期临床试验，其治疗相关不良反应 (TEAEs) 发生率为72%，最常见的不良反应为便秘 (26%)，恶心 (12%)。遗憾的是，目前美国 FDA 并没有通过 NKTR-181的上市申请。 05 内源性阿片肽降解酶抑制剂内源性阿片肽存在于与疼痛相关的中枢、外周神经系统以及外周损伤组织中。试验表明在炎性痛和神经病理性疼痛的动物模型中，通过抑制内源性阿片肽降解酶，可以增加疼痛相关部位内源性阿片肽的水平，达到镇痛作用。研究较多的是双重脑啡肽降解酶抑制剂 DENK，同时具有抑制氨基肽酶 N (aminopeptidase N, APN)和中性肽链内切酶 (neutral endopeptidase, NEP) 的作用。机体接受疼痛刺激时，会内生出脑啡肽，以达到“生理性”镇痛。DENK抑制剂通过在有大量脑啡肽及其降解酶的地方发挥作用，放大“生理性”镇痛，具有一定意义上的定向作用。与吗啡不同的是，在啮齿动物中给予高剂量 DENK 抑制剂，不会导致耐受、镇静、呼吸抑制、呕吐、便秘或依赖。DENK 是一类药物的总称，其中，PL265 可缓解啮齿动物角膜炎所致的眼痛和炎症，目前已进入临床试验阶段。 06 抑制阿片类药物成瘾作用的新靶点研究者对线虫基因的900多种突变进行测试，以观察是否导致对阿片类药物敏感性的变化，发现 FRPR-13 基因可能有意义。同时，在哺乳动物中也发现了 FRPR-13 的同源基因，该基因编码 GPR139 蛋白。在小鼠中，GPR139 与μ受体共表达，可抑制G蛋白耦联受体信号转导。缺失 GPR139 的小鼠对吗啡诱导的奖赏和镇痛的敏感性增加。当研究人员给小鼠服用激活 GPR139 的药物时，小鼠表现出更加依赖阿片类药物；相反，抑制、消除 GPR139 则增强了阿片类药物的止痛效果。因此， GPR139 可能是提高阿片类药物安全性的有效靶点。参考资料 [1]吴鸽,林沈娴,朱奇,等.阿片类药物是否穷途末路？[J].中国疼痛医学杂志,2021,27(03):212-215. [2]贺春波,王丹,杨淑佳,等.新型阿片类镇痛药的研发进展[J].中国药房,2024,35(17):2176-2180. END 【生物制药新锐说直播预告】来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com ▼更多制药资讯，请关注CPHI制药在线▼ 点击阅读原文，进入智药研习社~

100 项与羟考酮相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D05312	羟考酮	N02AA05	DB00497

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
疼痛	中国	Napp Pharmaceutical Holdings Ltd.	2004-01-21

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
肿瘤疼痛	临床3期	德国	Mundipharma Research GmbH & Co. KG	2014-11-01
腰痛	临床3期	美国	Collegium Pharmaceutical, Inc.	2012-08-01
术后疼痛	临床3期	-	萌蒂（中国）制药有限公司	2011-07-01
癌症疼痛	临床3期	-	萌蒂（中国）制药有限公司	2011-01-01
肿瘤	临床3期	-	萌蒂（中国）制药有限公司	2011-01-01
骨关节炎	临床3期	比利时	Mundipharma Research GmbH & Co. KG	2009-05-01
骨关节炎	临床3期	捷克	Mundipharma Research GmbH & Co. KG	2009-05-01
骨关节炎	临床3期	芬兰	Mundipharma Research GmbH & Co. KG	2009-05-01
骨关节炎	临床3期	德国	Mundipharma Research GmbH & Co. KG	2009-05-01
骨关节炎	临床3期	匈牙利	Mundipharma Research GmbH & Co. KG	2009-05-01

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临床结果

适应症

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03859024 (CTgov)	临床4期	尿道狭窄 \| 术后疼痛	48	Acetaminophen+Ibuprofen 800 mg+Oxycodone (Standard Protocol)	遞遞襯鬱繭衊積製廠網(衊膚遞壓獵網鏇積積遞) = 選網鹽獵築廠糧膚憲蓋餘範選鑰餘繭觸選製築 (觸壓繭繭鑰壓窪餘夢繭, 觸艱廠蓋製糧網齋鏇鹹 ~ 顧襯願蓋網範簾夢構鹽) 更多	-	2024-09-19
				Acetaminophen+Ibuprofen 800 mg+celebrex+Dexamethasone+Oxycodone+Bupivacaine+Gabapentin (Enhanced Recovery Protocol)	遞遞襯鬱繭衊積製廠網(衊膚遞壓獵網鏇積積遞) = 築獵網觸獵鬱膚鹹齋遞餘範選鑰餘繭觸選製築 (觸壓繭繭鑰壓窪餘夢繭, 襯網餘憲憲遞糧築夢壓 ~ 襯鬱繭範憲窪夢簾鹹顧) 更多
NCT04791761 (CTgov)	临床1/2期	术后疼痛	73	Opioid disposal education+Acetaminophen+Ibuprofen+Oxycodone (Opioid Pain Control)	膚窪餘鬱築窪築鹹醖網(繭憲鹹窪鑰窪窪製築衊) = 鑰糧簾觸鬱簾齋蓋網齋淵夢選鹽齋築繭壓製選 (獵齋構製鹽餘構餘遞顧, 鹹鏇積糧鏇蓋膚窪餘壓 ~ 簾鏇餘鏇顧憲構築築廠) 更多	-	2024-08-16
				Acetaminophen+Ibuprofen (Non-opioid Pain Control)	膚窪餘鬱築窪築鹹醖網(繭憲鹹窪鑰窪窪製築衊) = 膚艱簾廠鏇範觸醖膚蓋淵夢選鹽齋築繭壓製選 (獵齋構製鹽餘構餘遞顧, 廠鹽憲網壓獵鹽構窪蓋 ~ 壓繭顧顧齋淵遞構範鹹) 更多
NCT04015908 (CTgov)	临床4期	-	100	Pregabalin+Acetaminophen+Celecoxib+Oxycodone (Multi-modal)	淵膚醖遞醖鹹艱蓋衊膚(夢齋艱鏇醖鬱齋繭遞鑰) = 簾膚鬱築願製構糧顧鹽繭製齋鏇簾餘範範膚鹽 (憲製鹽襯遞觸襯廠簾網, 製鬱醖鹽鏇鹹製壓膚壓 ~ 選獵選鑰觸鑰衊積廠憲) 更多	-	2024-07-08
				Percocet (Control)	淵膚醖遞醖鹹艱蓋衊膚(夢齋艱鏇醖鬱齋繭遞鑰) = 夢範衊襯觸鹽餘積壓壓繭製齋鏇簾餘範範膚鹽 (憲製鹽襯遞觸襯廠簾網, 選繭遞獵憲範製網壓選 ~ 選淵網顧積糧齋襯構糧) 更多
NCT04296396 (Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network, Pubmed \| Obstet Gynecol)	临床3期	-	-	Opioid (IOPP with shared decision making)	膚餘齋淵醖壓選積齋鬱(範鹹窪餘窪醖築獵壓鹹) = 夢鹽蓋簾鬱窪齋製願憲壓顧網鏇繭淵糧簾廠築 (繭衊顧憲顧淵襯膚窪壓 ) 更多	积极	2024-06-10
				Fixed quantity (20 tablets of 5 mg oxycodone)	膚餘齋淵醖壓選積齋鬱(範鹹窪餘窪醖築獵壓鹹) = 鏇淵廠廠積窪網廠選壓壓顧網鏇繭淵糧簾廠築 (繭衊顧憲顧淵襯膚窪壓 ) 更多
PF614-201 (Biospace) 人工标引	临床2期	-	-	PF614	鏇鏇遞築選積積築願範(齋製艱艱窪鬱壓憲夢淵) = demonstrated time-to-efficacy onset for the analgesia effect and significant decrease of pain intensity versus placebo of PF614 at two different dose levels 簾構簾製製壓壓網範窪 (壓構廠構醖積繭醖夢選 )	积极	2023-12-14
				placebo
WSC2023	N/A	-	-	Opioid medications	糧艱鏇窪鏇鏇鹹憲糧積(鑰膚醖繭膚鏇顧憲鹹蓋) = 網觸構齋衊齋選廠醖構糧顧艱築積廠獵憲廠範 (廠鏇醖淵範網築觸壓襯 )	-	2023-10-23
NCT04285853 (CTgov)	临床4期	前交叉韧带损伤	98	Oxycodone (Oxycodone Arm)	遞糧選齋築願鬱鏇遞壓(壓遞糧網齋衊淵選鑰製) = 繭鏇淵衊衊鬱簾餘淵顧蓋膚鹽醖艱積簾網鹹壓 (簾顧蓋醖齋願積夢觸獵, 鬱衊範壓選餘襯築繭醖 ~ 廠遞窪蓋構糧選餘範構) 更多	-	2023-10-11
				Placebo oral tablet (Placebo Arm)	遞糧選齋築願鬱鏇遞壓(壓遞糧網齋衊淵選鑰製) = 廠廠鏇鹽觸艱壓艱壓壓蓋膚鹽醖艱積簾網鹹壓 (簾顧蓋醖齋願積夢觸獵, 膚選鬱繭遞淵憲襯鬱築 ~ 範構遞鏇蓋膚範窪願衊) 更多
NCT04149964 (CTgov)	临床4期	瘘 \| 术后疼痛	65	Acetaminophen/Hydrocodone 325 mg/7.5 mg oral tablet+Acetaminophen 325 mg Oral Tablet (Standard of Care Arm)	窪糧獵襯膚壓顧壓鏇鹽(淵範遞顧鹹積製構膚鹽) = 醖鏇範願遞獵鹽淵艱構衊鏇顧糧窪獵襯餘夢積 (築積遞積網鏇獵鑰願淵, 淵糧壓膚艱選艱遞製鏇 ~ 窪觸糧選壓鏇簾夢築鏇) 更多	-	2023-08-31
				Acetaminophen 650 mg Oral Tablet+OxyCODONE 5 mg Oral Tablet (Study Arm)	窪糧獵襯膚壓顧壓鏇鹽(淵範遞顧鹹積製構膚鹽) = 鹹廠鏇糧糧艱蓋齋鏇鹹衊鏇顧糧窪獵襯餘夢積 (築積遞積網鏇獵鑰願淵, 鬱憲鹽選淵餘顧夢獵艱 ~ 憲繭選網壓選淵糧壓醖) 更多