Development of Next-generation Pharmacotherapy for Opioid Use Disorders

开发治疗阿片类药物使用障碍的下一代药物疗法

基本信息

  • 批准号:
    10680546
  • 负责人:
  • 金额:
    $ 218.35万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-01-01 至 2025-07-31
  • 项目状态:
    未结题

项目摘要

ABSTRACT: This application in response to RFA-DA-19-002 proposes a phased plan that will fast track the IND development of a next-generation medication for opioid use disorders (OUD). The small-molecule compounds proposed for development are targeted to the nociceptin opioid receptor (NOP) and have shown promising efficacy in reducing oxycodone intake in nonhuman primates (rhesus monkeys) trained to self-administer oxycodone with efficacies similar to that of buprenorphine. But unlike buprenorphine, the NOP-targeted agonist lead compounds show no reinforcing effects by themselves, in monkeys. Also unlike buprenorphine and methadone, currently used for treating OUDs, NOP-targeted lead compounds do not produce physical dependence, tolerance, or respiratory depression, upon repeated administration. For the non-medical prescription opioid addiction, methadone and buprenorphine, both approved for illicit opioid (heroin) addiction treatment, are used. However, methadone, a mu opioid receptor (MOP) full agonist has significant abuse liability and causes withdrawal after chronic use, reliance on methadone clinics, and risk of drug overdose- induced respiratory depression. Buprenorphine (Bup), a MOP partial agonist and kappa opioid receptor (KOP) antagonist, produces limited respiratory depression; however, clinical studies indicate that it is less effective than methadone in reducing drug use, craving and relapse. Agonists targeted to the nociceptin/orphanin FQ peptide (NOP) receptor, the fourth opioid receptor subtype, modulate the pharmacology of MOP agonists and opioids, particularly in pain and reward circuitries. Our preliminary data shows that small-molecule NOP agonists reduce morphine-induced reward in rodents and this is further confirmed in our preliminary data in nonhuman primates, demonstrating promising anti-rewarding properties of a NOP/MOP partial agonist in decreasing oxycodone self-administration without producing dependence or respiratory depression. Together our data thus far suggests that the NOP agonists are a promising new approach to treat illicit and prescription opioid use disorders and may offer an alternative to buprenorphine use. In the UG3 phase of this project, we propose to conduct non-GLP ADME-tox and efficacy confirmation, and additional lead optimization if warranted, with the goal/milestone being the nomination of a `IND candidate' and backup candidates, for IND-enabling studies and an IND filing (in the UH3phase).
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项目成果

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Nurulain T Zaveri其他文献

Nurulain T Zaveri的其他文献

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{{ truncateString('Nurulain T Zaveri', 18)}}的其他基金

Development of Next-generation Pharmacotherapy for Opioid Use Disorders
开发治疗阿片类药物使用障碍的下一代药物疗法
  • 批准号:
    10655111
  • 财政年份:
    2019
  • 资助金额:
    $ 218.35万
  • 项目类别:
DEVELOPMENT OF A NOVEL DRUG CANDIDATE WITH A FIRST-in-CLASS MECHANISM FOR SMOKING CESSATION, RELAPSE and ABSTINENCE
开发具有一流戒烟、复吸和戒烟机制的新型候选药物
  • 批准号:
    9788405
  • 财政年份:
    2018
  • 资助金额:
    $ 218.35万
  • 项目类别:
PRECLINICAL DEVELOPMENT OF NOVEL SMOKING CESSATION PHARMACOTHERAPIES
新型戒烟药物的临床前开发
  • 批准号:
    8715436
  • 财政年份:
    2014
  • 资助金额:
    $ 218.35万
  • 项目类别:
PRECLINICAL DEVELOPMENT OF NOVEL SMOKING CESSATION PHARMACOTHERAPIES
新型戒烟药物的临床前开发
  • 批准号:
    8848367
  • 财政年份:
    2014
  • 资助金额:
    $ 218.35万
  • 项目类别:
Development of Novel Drugs for Smoking Cessation Pharmacotherapy
戒烟药物治疗新药的开发
  • 批准号:
    8315565
  • 财政年份:
    2012
  • 资助金额:
    $ 218.35万
  • 项目类别:
A NOVEL APPROACH FOR PAIN TREATMENT WITHOUT OPIOID LIABILITIES
一种没有阿片类药物副作用的疼痛治疗新方法
  • 批准号:
    9270527
  • 财政年份:
    2012
  • 资助金额:
    $ 218.35万
  • 项目类别:
Analgesic Potential of NOP Agonists to Treat Pain in Sickle Cell Disease
NOP 激动剂治疗镰状细胞病疼痛的镇痛潜力
  • 批准号:
    8394806
  • 财政年份:
    2012
  • 资助金额:
    $ 218.35万
  • 项目类别:
Development of Novel Therapies for Levodopa-induced Dyskinesia in Parkinson's Dis
帕金森病左旋多巴诱发的运动障碍新疗法的开发
  • 批准号:
    7927877
  • 财政年份:
    2010
  • 资助金额:
    $ 218.35万
  • 项目类别:
Discovery of Bifunctional NOP/Opioid Receptor Ligands for Drug Abuse Therapy
用于药物滥用治疗的双功能 NOP/阿片受体配体的发现
  • 批准号:
    8848273
  • 财政年份:
    2009
  • 资助金额:
    $ 218.35万
  • 项目类别:
Discovery of Bifunctional NOP/Opioid Receptor Ligands for Drug Abuse Therapy
用于药物滥用治疗的双功能 NOP/阿片受体配体的发现
  • 批准号:
    7767102
  • 财政年份:
    2009
  • 资助金额:
    $ 218.35万
  • 项目类别:

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