Cannabinergic Receptor Antagonists for Nicotine Addiction

大麻素受体拮抗剂治疗尼古丁成瘾

基本信息

批准号：
8713752
负责人：
Shakiru Olajire Alapafuja
金额：
$ 22.18万
依托单位：
MAKSCIENTIFIC, LLC
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-01 至 2015-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8713752
关键词：
Address Adverse effects Affinity Agonist Anhedonia Animals Attenuated Back Behavioral Binding Biological Assay Biological Availability Brain CNR1 gene Cannabinoids Chemistry Clinical Computer Simulation Development Discrimination Distress Dose Evaluation Exhibits Goals Health Hazards Hepatic Hospitals Human In Vitro Intention Laboratories Lead Legal patent Letters Ligands Liver Microsomes Measures Metabolic Microsomes Modeling Motor Activity Mus Nicotine Nicotine Dependence Nicotinic Agonists Oral Penetration Pharmaceutical Preparations Pharmacotherapy Phase Property Public Health Publishing Pyrazoles Pyrrolidinones Rattus Relative (related person)Research Resistance Rewards Rodent Selection Criteria Self Administration Series Smoking Stimulus Structure Taste Perception Testing Therapeutic Time Universities Work addiction analog attenuation base combat commercialization design drug discovery in vivo liquid chromatography mass spectrometry man nonhuman primate novel novel strategies pharmacophore phase 2 study pre-clinical preclinical study programs public health relevance receptor rimonabant screening smoking cessation success varenicline

项目摘要

DESCRIPTION (provided by applicant): Existing evidence in animals and man indicates that blockade of the CB1 receptor may offer an effective approach for combating nicotine addiction. Early studies in humans have documented these effects. This Phase I application proposes studies to design advanced CB1 pyrrolidinone antagonists toward the development of medications for smoking cessation. Our intention is to: 1) develop CB1 antagonists with limited inverse agonist or neutral antagonist activity and 2) to characterize their ability to attenuate th effects of nicotine in behavioral screening assays in rats that can be conducted within the limits of a Phase I program. We expect to forward the most successful compounds from Phase I into Phase II studies, in which we shall pursue a more detailed lead optimization program, characterize compounds for side-effect liability, and evaluate their ability to reduce addiction-related effects of nicotine in established, addiction-related, self- administration studies in nonhuman primates. Such Phase II studies should lead to one pre-clinical candidate and 2-3 back-ups.

描述（由申请人提供）：动物和人类的现有证据表明，阻断 CB1 受体可能为对抗尼古丁成瘾提供有效的方法。早期对人类的研究已经记录了这些影响。该一期申请提出了设计先进 CB1 吡咯烷酮拮抗剂的研究，以开发戒烟药物。我们的目的是：1) 开发具有有限反向激动剂或中性拮抗剂活性的 CB1 拮抗剂，2) 在大鼠行为筛选试验中表征其减弱尼古丁影响的能力，这些试验可在 I 期计划的范围内进行。我们期望将最成功的化合物从第一阶段研究推进到第二阶段研究，其中我们将追求更详细的先导优化计划，表征化合物的副作用倾向，并评估它们在已建立的药物中减少尼古丁成瘾相关影响的能力。，在非人类灵长类动物中进行的与成瘾相关的自我给药研究。此类 II 期研究应产生一名临床前候选药物和 2-3 名备用药物。