Pioglitazone for the Treatment of Opioid and of Nicotine Dependence

吡格列酮用于治疗阿片类药物和尼古丁依赖

基本信息

批准号：
8487385
负责人：
ADAM BISAGA
金额：
$ 83.35万
依托单位：
NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-30 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8487385
关键词：
Abstinence Adult Agonist Area Behavior Behavioral Buprenorphine Cigarette Cigarette Smoker Cognitive Combination Medication Cues Data Dependence Development Diabetes Mellitus Dose Double-Blind Method Drug Addiction Drug abuse Drug usage Effectiveness FDA approved Focus Groups Goals Heroin Heroin Abuse Human Individual Inpatients Investigation Laboratories Laboratory Study Life Marketing Measures Methadone Microglia Minocycline Modeling Morphine Naloxone Neuroglia Nicotine Nicotine Dependence Nicotine Withdrawal Nicotinic Receptors Non-Insulin-Dependent Diabetes Mellitus Opiate Addiction Opioid Opioid Receptor PPAR gamma Participant Pathway interactions Patients Performance Pharmaceutical Preparations Pharmacotherapy Physiological Pioglitazone Placebo Control Placebos Play Prevalence Randomized Rattus Relapse Replacement Therapy Research Resistance Rewards Role Rolipram Safety Self Administration Series Severities Smoking Social Problems Stress Substance abuse problem Takeda brand of pioglitazone hydrochloride Testing Therapy Clinical Trials Tobacco use Toxic effect Treatment Effectiveness Yohimbine base cigarette smoking compare effectiveness craving design drug craving drug maintenance drug of abuse improved inhibitor/antagonist macrophage monocyte nicotine patch nicotine replacement novel opioid abuse opioid withdrawal pre-clinical preclinical study prescription opioid prescription opioid abuse prevent public health relevance response treatment strategy varenicline volunteer

项目摘要

DESCRIPTION (provided by applicant): Currently, the abuse of heroin and prescription opioid medications is a pervasive social problem in the U.S. Similarly, the prevalence of tobacco use among adults in the U.S. is approximately 20%, despite intensive efforts to reduce its use. We are proposing to test the ability of pioglitazone, a peroxisome proliferator-activated receptor- gamma (PPAR) agonist that is FDA-approved for use in the management of type 2 diabetes mellitus, to reduce abuse of heroin (Study 1), and cigarette smoking (Study 2). Pioglitazone will be tested in combination with buprenorphine/naloxone (Study 1) and with the nicotine patch (Study 2). These studies were based on a series of unpublished preclinical data showing that pioglitazone may have utility in treating opioid and nicotine dependence. Participants in all studies will live on a locked inpatient unit and will be tested in the laboratory. The ability of pioglitazone to alter drug self-administration, reactivity to drug cues, and relapse to drug use will be assessed. In addition, subjective responses, such as ratings of drug liking, craving, and desire to take the drug again will be evaluated. Potential toxicity of the medication combinations will be assessed by measuring cognitive performance and physiological responses. The results of these studies will provide a great deal of information about the effects of pioglitazone in combination with agonist replacement therapies. If the results of the proposed studies support the preclinical data with pioglitazone, they may reveal a previously unidentified target for medications development for substance abuse.

描述（由申请人提供）：目前，在美国，滥用海洛因和处方阿片类药物是一个普遍的社会问题，尽管美国成年人在美国成年人中使用烟草的流行率约为20％，尽管减少其使用量。我们提议测试Pioglitazone（一种过氧化物酶体增殖物激活的受体γ（PPAR）激动剂，该激动剂是FDA批准的，用于管理2型糖尿病的管理，以减少海洛因（研究1）的滥用（研究1）和吸烟（研究2）。吡格列酮将与丁丙诺啡/纳洛酮（研究1）和尼古丁斑（研究2）结合测试。这些研究基于一系列未发表的临床前数据，表明吡格列酮可能在治疗阿片类药物和尼古丁依赖性方面具有实用性。所有研究的参与者将生活在一个锁定的住院单元上，并将在实验室进行测试。吡格列酮改变药物自我给药，对药物提示的反应性以及对药物使用的复发的能力将得到评估。此外，将评估主观反应，例如药物喜欢，渴望和渴望再次服用药物的评级。药物组合的潜在毒性将通过测量认知能力和生理反应来评估。这些研究的结果将提供有关吡格列酮与激动剂替代疗法的影响的大量信息。如果拟议研究的结果支持吡格列酮的临床前数据，则可能会揭示以前未识别的药物开发量的药物滥用靶标。

项目成果

期刊论文数量（2）

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 PPARγ Agonist Pioglitazone Fails to Alter the Abuse Potential of Heroin, But Does Reduce Heroin Craving and Anxiety.

PPARγ 激动剂吡格列酮无法改变海洛因的滥用潜力，但可以减少海洛因的渴望和焦虑。

DOI：
10.1080/02791072.2018.1508789
发表时间：
2018
期刊：
Journal of psychoactive drugs
影响因子：
2.8
作者：
Jones,JermaineD;Bisaga,Adam;Metz,VerenaE;Manubay,JeanneM;Mogali,Shanthi;Ciccocioppo,Roberto;Madera,Gabriela;Doernberg,Molly;Comer,SandraD
通讯作者：
Comer,SandraD

The effects of heroin administration and drug cues on impulsivity.