TAAR1 agonists for nicotine addiction

TAAR1 激动剂治疗尼古丁成瘾

基本信息

  • 批准号:
    10561715
  • 负责人:
  • 金额:
    $ 39.55万
  • 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:
    2019-04-01 至 2025-02-28
  • 项目状态:
    未结题

项目摘要

ABSTRACT Tobacco smoking remains a major public health concern globally. Although there are FDA-approved therapeutic options available, they are far from adequate to maintain long-term smoking abstinence in most smokers. Thus, discovering novel efficacious pharmacotherapies to aid in smoking cessation remains an urgent clinical need. Nicotine, the major component in tobacco that is responsible for tobacco addiction, stimulates the mesolimbic dopaminergic system via activating nicotinic acetylcholine receptors (nAChRs). Nicotine replacement therapy and the nAChR partial agonist varenicline have achieved limited clinical success by directly modulating the central nAChRs. Indirect modulation of dopaminergic system by non-dopaminergic mechanism may also be able to modulate the addiction-related effects of nicotine. Trace amine associated receptor 1 (TAAR1) has emerged as a novel target for the development of potential pharmacotherapy to treat drug addiction. In particular, our preliminary data have shown that acute TAAR1 agonist treatment is able to reduce some addiction-related effects of nicotine. The objective of the present application is to systematically assess the therapeutic potential of TAAR1 agonists on nicotine addiction. Three Specific Aims are proposed: Aim 1 will examine the effects of repeated TAAR1 agonists (full agonist RO5166017 and partial agonist RO5263397) treatment on nicotine reinforcement using a short-access (1 hour) nicotine self-administration paradigm; Aim 2 will examine the effects of TAAR1 agonists on the reinstatement and incubation of nicotine- seeking behavior in rats with a long-access (21 hours) nicotine self-administration history; Aim 3 will examine the effects of TAAR1 agonists on nicotine withdrawal in rats with a long-access (21 hours) nicotine self- administration history. Collectively, the proposed studies systematically evaluate the effects of TAAR1 agonists on four critical aspects of nicotine addiction (e.g., reinforcing effects, reinstatement, incubation and withdrawal symptoms), each of which is thought to contribute significantly to nicotine dependence and relapse. Successful execution of the proposed studies will confirm the essential role TAAR1 in mediating nicotine addiction and provide critical preclinical evidence in support of developing TAAR1 agonists are novel pharmacotherapy for smoking cessation.
摘要

项目成果

期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
The selective TAAR1 partial agonist RO5263397 promoted novelty recognition memory in mice.
  • DOI:
    10.1007/s00213-021-05937-1
  • 发表时间:
    2021-11
  • 期刊:
  • 影响因子:
    3.4
  • 作者:
    Wu R;Liu J;Seaman R Jr;Johnson B;Zhang Y;Li JX
  • 通讯作者:
    Li JX
Toll-Like Receptor 4: A Novel Target to Tackle Drug Addiction?
Toll 样受体 4:解决毒瘾问题的新靶点?
Potential of Ligands for Trace Amine-Associated Receptor 1 (TAAR1) in the Management of Substance Use Disorders.
  • DOI:
    10.1007/s40263-021-00871-4
  • 发表时间:
    2021-12
  • 期刊:
  • 影响因子:
    6
  • 作者:
    Wu R;Li JX
  • 通讯作者:
    Li JX
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Jun-Xu Li其他文献

Jun-Xu Li的其他文献

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{{ truncateString('Jun-Xu Li', 18)}}的其他基金

Development of LPA5 Antagonists as Analgesics
LPA5 拮抗剂镇痛药的开发
  • 批准号:
    10638278
  • 财政年份:
    2023
  • 资助金额:
    $ 39.55万
  • 项目类别:
TAAR1 agonists for nicotine addiction
TAAR1 激动剂治疗尼古丁成瘾
  • 批准号:
    9892992
  • 财政年份:
    2019
  • 资助金额:
    $ 39.55万
  • 项目类别:
TAAR1 agonists for nicotine addiction
TAAR1 激动剂治疗尼古丁成瘾
  • 批准号:
    10353373
  • 财政年份:
    2019
  • 资助金额:
    $ 39.55万
  • 项目类别:
TAAR1 agonists for nicotine addiction
TAAR1 激动剂治疗尼古丁成瘾
  • 批准号:
    10092996
  • 财政年份:
    2019
  • 资助金额:
    $ 39.55万
  • 项目类别:
TAAR 1 modulation of addiction-related effects of nicotine
TAAR 1 调节尼古丁成瘾相关效应
  • 批准号:
    9182100
  • 财政年份:
    2016
  • 资助金额:
    $ 39.55万
  • 项目类别:
TAAR 1 modulation of addiction-related effects of nicotine
TAAR 1 调节尼古丁成瘾相关效应
  • 批准号:
    9307798
  • 财政年份:
    2016
  • 资助金额:
    $ 39.55万
  • 项目类别:
Imidazoline I2 receptors as targets for the treatment of pain
咪唑啉 I2 受体作为治疗疼痛的靶点
  • 批准号:
    9186516
  • 财政年份:
    2013
  • 资助金额:
    $ 39.55万
  • 项目类别:
IMIDAZOLINE I2 RECEPTORS AS TARGETS FOR THE TREATMENT OF PAIN
咪唑啉 I2 受体作为治疗疼痛的靶点
  • 批准号:
    9170057
  • 财政年份:
    2013
  • 资助金额:
    $ 39.55万
  • 项目类别:
Imidazoline I2 receptors as targets for the treatment of pain
咪唑啉 I2 受体作为治疗疼痛的靶标
  • 批准号:
    8970695
  • 财政年份:
    2013
  • 资助金额:
    $ 39.55万
  • 项目类别:
Behavioral effects of methamphetamine & imidazoline I2 receptor ligands
甲基苯丙胺对行为的影响
  • 批准号:
    8581533
  • 财政年份:
    2013
  • 资助金额:
    $ 39.55万
  • 项目类别:

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阐明滥用 CB1 受体激动剂引起的急性中毒机制。
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  • 批准号:
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