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
- 来源:
- 关键词:AbstinenceAcuteAgonistAminesAttenuatedBehaviorBehavioralBupropionCessation of lifeClinicalCocaineCuesDataDevelopmentDiseaseDopamineDoseDrug AddictionExtinctionFDA approvedFemaleFilamentFoodHealth Care CostsHourHyperalgesiaIncubatedInfusion proceduresIntravenousMaintenanceMecamylamineMechanicsMediatingMethamphetamineMissionNicotineNicotine DependenceNicotine WithdrawalNicotinic AgonistsNicotinic ReceptorsPharmaceutical PreparationsPharmacotherapyProtocols documentationPsychological reinforcementPublic HealthRattusRecording of previous eventsRegimenRelapseResearchRoleScheduleSelf AdministrationSex DifferencesSmokerSmokingSystemTestingTherapeuticTobaccoTobacco DependenceTobacco smoking behaviorTobacco useTrainingUnited States National Institutes of HealthWithdrawalWithdrawal Symptomaddictionanxiety-like behaviorcombatcost effectiveefficacious treatmentexperienceinhibitorlong term abstinencemalemen&aposs groupmonoaminemortality risknicotine replacementnicotine seeking behaviornicotine self-administrationnovelpharmacologicpre-clinicalreceptorreuptakesmoking abstinencesmoking cessationsuccesstransmission processvarenicline
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?
- DOI:10.1007/164_2022_586
- 发表时间:2022
- 期刊:
- 影响因子:0
- 作者:Liu,Jianfeng;Li,Jun-Xu;Wu,Ruyan
- 通讯作者:Wu,Ruyan
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
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Jun-Xu Li其他文献
Jun-Xu Li的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ 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:
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:
相似海外基金
Elucidation of acute poisoning mechanism due to abuse of CB1 receptor agonist.
阐明滥用 CB1 受体激动剂引起的急性中毒机制。
- 批准号:
21K17323 - 财政年份:2021
- 资助金额:
$ 39.55万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Elucidation of acute poisoning mechanism due to abuse of CB1 receptor agonist.
阐明滥用 CB1 受体激动剂引起的急性中毒机制。
- 批准号:
19K19485 - 财政年份:2019
- 资助金额:
$ 39.55万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Tissue repair effect in acute myocardial infarction through mobilization of endogenous Muse cells by sphingosine-1-phosphate receptor 2 agonist
1-磷酸鞘氨醇受体2激动剂动员内源性Muse细胞对急性心肌梗死的组织修复作用
- 批准号:
18K15843 - 财政年份:2018
- 资助金额:
$ 39.55万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
EFFECT OF ACUTE E PROSTAGLANDIN AGONIST N BAL EICO
急性 E 型前列腺素激动剂 N BAL EICO 的作用
- 批准号:
6115624 - 财政年份:1998
- 资助金额:
$ 39.55万 - 项目类别:
EFFECT OF ACUTE E PROSTAGLANDIN AGONIST N BAL EICO
急性 E 型前列腺素激动剂 N BAL EICO 的作用
- 批准号:
6219539 - 财政年份:1998
- 资助金额:
$ 39.55万 - 项目类别:
EFFECT OF ACUTE E PROSTAGLANDIN AGONIST N BAL EICO
急性 E 型前列腺素激动剂 N BAL EICO 的作用
- 批准号:
6276858 - 财政年份:1997
- 资助金额:
$ 39.55万 - 项目类别:
ACUTE CHRONIC HORMONAL CHANGES WITH LHRH-AGONIST THERAPY
LHRH 激动剂治疗引起的急性慢性荷尔蒙变化
- 批准号:
6250152 - 财政年份:1997
- 资助金额:
$ 39.55万 - 项目类别:
ACUTE CHRONIC HORMONAL CHANGES WITH LHRH-AGONIST THERAPY
LHRH 激动剂治疗引起的急性慢性荷尔蒙变化
- 批准号:
6279945 - 财政年份:1997
- 资助金额:
$ 39.55万 - 项目类别:
EFFECT OF ACUTE E PROSTAGLANDIN AGONIST N BAL EICO
急性 E 型前列腺素激动剂 N BAL EICO 的作用
- 批准号:
6246787 - 财政年份:1997
- 资助金额:
$ 39.55万 - 项目类别:
PSYCHOPHARMACOLOGY OF DA AGONIST CNS EFFECTS: ACUTE AND CHRONIC STUDIES
DA 激动剂中枢神经系统影响的精神药理学:急性和慢性研究
- 批准号:
3891471 - 财政年份:
- 资助金额:
$ 39.55万 - 项目类别: