主要研究目的：研究空腹状态下单次舌下含服受试制剂丁丙诺啡纳洛酮舌下片（规格：8mg/2mg，宜昌人福药业有限责任公司生产）与参比制剂丁丙诺啡纳洛酮舌下片（商品名：Suboxone ，规格：8mg/2mg；Indivior Europe Limited持证）在健康受试者体内的药代动力学，评价空腹状态使用两种制剂的生物等效性。次要研究目的：评价受试制剂丁丙诺啡纳洛酮舌下片（规格：8mg/2mg）和参比制剂丁丙诺啡纳洛酮舌下片（商品名：Suboxone ，规格：8mg/2mg）在健康受试者中的安全性。

开始日期2024-10-06

申办/合作机构

宜昌人福药业有限责任公司

NCT05450718 / Recruiting临床4期IIT

A Pilot Randomized Controlled Trial of Low-dose Buprenorphine Initiation for Opioid Use Disorder

The purpose of this study is to test whether low-dose buprenorphine initiation for treatment of opioid use disorder is safe and effective.

开始日期2024-10-01

申办/合作机构

Montefiore Medical Center

NCT06576843 / Recruiting临床2期

An Open-label, Multicentre Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Repeated Doses of INDV-6001 in Adults with Moderate to Severe Opioid Use Disorder

The current study will evaluate the pharmacokinetics, safety, and tolerability of INDV-6001 following multiple doses in participants with opioid use disorder in order to select optimum dosing regimens for future studies. Prior to receiving INDV-6001, participants will be stabilised on 12-16 mg of transmucosal BUP (SUBOXONE®) or will transition from a monthly maintenance dose of subcutaneous extended-release BUP (SUBLOCADE®). This study will also evaluate the use of alternative injection sites (thigh, back of upper arm), which may be desirable in this patient population for the anticipated extended durations of treatment.

开始日期2024-09-17

申办/合作机构

Indivior, Inc.

100 项与 κ opioid receptor x OOR x μ opioid receptor 相关的临床结果

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100 项与 κ opioid receptor x OOR x μ opioid receptor 相关的转化医学

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0 项与 κ opioid receptor x OOR x μ opioid receptor 相关的专利（医药）

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项与 κ opioid receptor x OOR x μ opioid receptor 相关的文献（医药）

2018-11-01·Phytomedicine2区 · 医学

Curcumin downregulates expression of opioid-related nociceptin receptor gene (OPRL1) in isolated neuroglia cells

2区 · 医学

Article

作者: Efferth, Thomas ; Panossian, Alexander ; Seo, Ean-Jeong

BACKGROUNDCurcumin (CC) exerts polyvalent pharmacological actions and multi-target effects, including pain relief and anti-nociceptive activity. In combination with Boswellia serrata extract (BS), curcumin shows greater efficacy in knee osteoarthritis management, presumably due to synergistic interaction of the ingredients.AIMTo elucidate the molecular mechanisms underlying the analgesic activity of curcumin and its synergistic interaction with BS.METHODSWe performed gene expression profiling by transcriptome-wide mRNA sequencing in human T98G neuroglia cells treated with CC (Curamed), BS, and the combination of CC and BS (CC-BS; Curamin), followed by interactive pathways analysis of the regulated genes.RESULTSTreatment with CC and with CC-BS selectively downregulated opioid-related nociceptin receptor 1 gene (OPRL1) expression by 5.9-fold and 7.2-fold, respectively. No changes were detected in the other canonical opioid receptor genes: OPRK1, OPRD1, and OPRM1. Nociceptin reportedly increases the sensation of pain in supra-spinal pain transduction pathways. Thus, CC and CC-BS may downregulate OPRL1, consequently inhibiting production of the nociception receptor NOP, leading to pain relief. In neuroglia cells, CC and CC-BS inhibited signaling pathways related to opioids, neuropathic pain, neuroinflammation, osteoarthritis, and rheumatoid diseases. CC and CC-BS also downregulated ADAM metallopeptidase gene ADAMTS5 expression by 11.2-fold and 13.5-fold, respectively. ADAMTS5 encodes a peptidase that plays a crucial role in osteoarthritis development via inhibition of a corresponding signaling pathway.CONCLUSIONHere, we report for the first time that CC and CC-BS act as nociceptin receptor antagonists, selectively downregulating opioid-related nociceptin receptor 1 gene (OPRL1) expression, which is associated with pain relief. BS alone did not affect OPRL1 expression, but rather appears to potentiate the effects of CC via multiple mechanisms, including synergistic interactions of molecular networks.

2018-07-01·British Journal of Pharmacology2区 · 医学

Allostery at opioid receptors: modulation with small molecule ligands

2区 · 医学

Review

作者: Traynor, John R ; Livingston, Kathryn E

Opioid receptors are 7‐transmembrane domain receptors that couple to heterotrimeric G proteins. The endogenous ligands for opioid receptors are peptides which bind to the orthosteric site on the receptors. The μ‐opioid receptor is the target for opioid analgesics, while the δ‐opioid receptor has been suggested as a target for pain management, migraine and depression. Similarly, κ‐opioid receptors are involved in pain and depression and nociceptin receptors in pain and mood behaviours. However, exogenous orthosteric ligands for opioid receptors cause a myriad of on‐target side effects. Recently, selective allosteric ligands for μ‐ and δ‐opioid receptors have been described. These compounds bind to a site on the receptor distinct from the orthosteric site. Occupation of this allosteric site leads to modulation of orthosteric ligand binding affinity and/or efficacy. Allosteric modulators may be positive, negative or silent (neutral) (PAMs, NAMs or SAMs respectively). PAMs may have in vivo activity by enhancing the activity of exogenous drugs or endogenous opioid peptides. Enhancing endogenous opioid peptide activity maintains the temporal and spatial distribution of these molecules but improves, and potentially qualitatively changes, activity at their cognate receptors which could limit side effects compared with traditional opioid drugs. In this review, we describe the rationale and promise for the development of allosteric modulators for opioid receptors, the discovery of selective allosteric modulators, the identification of potential allosteric sites on opioid receptors and the mode of action of the modulators.Linked ArticlesThis article is part of a themed section on Emerging Areas of Opioid Pharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.14/issuetoc

2018-07-01·British Journal of Pharmacology2区 · 医学

Targeting multiple opioid receptors – improved analgesics with reduced side effects?

2区 · 医学

Review

作者: Kliewer, Andrea ; Mann, Anika ; Dasgupta, Pooja ; Miess, Elke ; Günther, Thomas ; Fritzwanker, Sebastian ; Schulz, Stefan ; Steinborn, Ralph

Classical opioid analgesics, including morphine, mediate all of their desired and undesired effects by specific activation of the μ‐opioid receptor (μ receptor). The use of morphine for treating chronic pain, however, is limited by the development of constipation, respiratory depression, tolerance and dependence. Analgesic effects can also be mediated through other members of the opioid receptor family such as the κ‐opioid receptor (κ receptor), δ‐opioid receptor (δ receptor) and the nociceptin/orphanin FQ peptide receptor (NOP receptor). Currently, a new generation of opioid analgesics is being developed that can simultaneously bind with high affinity to multiple opioid receptors. With this new action profile, it is hoped that additional analgesic effects and fewer side effects can be achieved. Recent research is mainly focused on the development of bifunctional μ/NOP receptor agonists, which has already led to novel lead structures such as the spiroindole‐based cebranopadol and a compound class with a piperidin‐4‐yl‐1,3‐dihydroindol‐2‐one backbone (SR16835/AT‐202 and SR14150/AT‐200). In addition, the ornivol BU08028 is an analogue of the clinically well‐established buprenorphine. Moreover, the morphinan‐based nalfurafine exerts its effect with a dominant κ receptor‐component and is therefore utilized in the treatment of pruritus. The very potent dihydroetorphine is a true multi‐receptor opioid ligand in that it binds to μ, κ and δ receptors. The main focus of this review is to assess the paradigm of opioid ligands targeting multiple receptors with a single chemical entity. We reflect on this rationale by discussing the biological actions of particular multi‐opioid receptor ligands, but not on their medicinal chemistry and design.Linked ArticlesThis article is part of a themed section on Emerging Areas of Opioid Pharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.14/issuetoc

项与 κ opioid receptor x OOR x μ opioid receptor 相关的新闻（医药）

2024-07-30

·Business Wire

Tris Pharma to Present New Safety Data for First-In-Class Investigational Pain Therapy and Host Symposium at the International Association for the Study of Pain (IASP) 2024 World Congress on Pain

MONMOUTH JUNCTION, N.J.--( BUSINESS WIRE )--Tris Pharma, Inc. (Tris), a commercial-stage biopharmaceutical company focused on attention deficit hyperactivity disorder (ADHD), pain, addiction and neurological disorders, today announced that the company will present data from its first-in-class, late-stage investigational pain therapy with a novel mechanism of action, cebranopadol, at the upcoming International Association for the Study of Pain (IASP) 2024 World Congress on Pain, taking place August 5-9, 2024, in Amsterdam. “I am inspired to see the rise in interest, funding and research into the development of novel treatment options for the millions of people who suffer daily from debilitating pain that impacts their quality of life,” said Ketan Mehta, founder and CEO at Tris Pharma. “Our team has been working with urgency to advance cebranopadol, a first-in-class investigational pain therapy with a novel mechanism of action, through clinical studies with the goal of offering physicians an effective treatment option that they can confidently prescribe and patients feel is safe. We look forward to collaborating with the pain community at IASP 2024 and sharing our latest findings.” Cebranopadol is the first and only dual nociceptin/orphanin FQ peptide (NOP) receptor and µ-opioid peptide (MOP) receptor (dual-NMR) agonist in development to treat moderate-to-severe pain. Dual-NMR agonist compounds have the potential to deliver gold-standard pain relief with a strong safety profile because they mimic the body’s natural pain-modulation processes by synergizing the analgesic and safety characteristics of the NOP receptor with the analgesic advantages of the MOP receptor. Tris Pharma plans to share important news regarding its Phase 3 clinical trials in the near future. Symposium Highlighting Novel Pain Mechanism Tris Pharma will host a symposium featuring a series of presentations focused on dual-NMR agonists, a promising new mechanism of action in treating pain, and its potential to overcome the shortfalls of opioids for moderate-to-severe pain. The symposium will be presented as part of the congress by leading scientists with extensive experience in the research and development of novel pain therapies. Details of the symposium are as follows: Symposium: Break the Mold in Pain Biology: The Promise of a New Mechanism that May Overcome the Shortfalls of Current Moderate to Severe Pain Medications Presenters: Charles E. Argoff, MD, Albany Medical College; Roberto Ciccocioppo, PhD, University of Camerino; Jeffrey Gudin, MD, University of Miami Miller School of Medicine Location: RAI Amsterdam Convention Centre, Elicium I Date and Time: August 6, 12:45 – 1:45 p.m. CEST At IASP 2024 Tris Pharma will be present at Booth #316 where company executives will be available to provide additional information and data presented at the congress. About Cebranopadol (TRN-228) Cebranopadol is the first and only investigational dual nociceptin/orphanin FQ peptide (NOP) receptor and µ-opioid peptide (MOP) receptor (dual-NMR) agonist for the treatment of moderate-to-severe pain, as well as opioid use disorder (OUD). Cebranopadol offers a first of its kind and novel mechanism of action that takes advantage of the inherent properties of the NOP receptor, which has demonstrated both the potential to lessen the risk of misuse while still providing effective pain relief, and the potential to block drugs of abuse from producing drug-seeking behaviors. The FDA has granted Fast Track Designation to cebranopadol for chronic low back pain. Cebranopadol’s profile has been well-characterized in pain management studies, and if approved, it could become the first and only pain-relief therapy with the demonstrated ability to provide efficacy equivalent to opioids with significantly less risk for misuse or risk of physical dependence, addiction or overdose. About Tris Pharma Tris Pharma is a privately held, innovation-driven biopharmaceutical company that is applying its drug development capabilities and proprietary technologies to transform the treatment of ADHD, pain and neurological disorders, including addiction and diseases of the central nervous system. Tris is an established commercial organization with a robust portfolio of best-in-class ADHD products and a promising pipeline of differentiated, near-term drug candidates. More information is available at www.trispharma.com and on LinkedIn @ TrisPharma .

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