Development of a preclinical candidate for the treatment of alcoholism

开发治疗酒精中毒的临床前候选药物

• 批准号: 8901731
• 负责人: Richard M. van Rijn
• 金额: $ 23.74万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-05 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8901731
• 关键词: Adverse effects; Affect; Agonist; Alcohol abuse; Alcohol consumption; Alcohol withdrawal syndrome; Alcoholism; Alcohols; Anti-Anxiety Agents; Anxiety; Binding; Biological Assay; Chronic; Development; Disease; Drug Interactions; Drug Targeting; Drug usage; Ethanol; FDA approved; G-Protein-Coupled Receptors; Goals; Hyperalgesia; In Vitro; Individual; Intervention; Lead; Left; Ligands; Methods; Molecular; Mus; Naltrexone; Nature; Opioid; Opioid Receptor; Pharmaceutical Preparations; Pharmacology; Physiological; Play; Population Heterogeneity; Property; Relapse; Research; Rewards; Role; Societies; Stimulus; Testing; Therapeutic; Time; abstracting; alcohol behavior; alcohol exposure; alcoholism therapy; clinically relevant; delta opioid receptor; design; drinking; drinking behavior; drug efficacy; in vitro Assay; in vivo; mouse model; novel; pre-clinical; preference; radioligand; receptor; response; screening; withdrawal-induced anxiety

Project Summary/Abstract Alcoholism and alcohol related illnesses put a large strain on society. While therapeutics are available, none are universally effective among the diverse population of treatment seeking individuals. My research is focused on elucidating the role of two delta opioid receptor subtypes (DOR1 and DOR2) in alcohol abuse disorders. Their ability to affect both ethanol consumption and anxiety make these DOR subtypes promising potential novel drug targets to treat alcoholism. So far I have discovered that the DOR subtypes have unique and sometimes opposing effects on ethanol consumption and anxiety. Moreover, I determined that the DOR1's pharmacology may result from an interaction of the DOR with the MOR forming a DOR-MOR heteromer. My research is designed to determine the mechanism behind the unique pharmacology of the DOR subtypes and exploit it to develop novel drugs that can treat alcohol abuse disorders better and with fewer side effects than the currently available medication. One integral part of my research is resolving how chronic ethanol exposure results in an increase in the number of functional DORs. Additionally, I have designed a unique method to identify drugs that selectively interact with receptor heteromers using a high throughput in vitro assay. I intend to further test compounds identified in this assay using mice models of alcoholism, determining their effects on ethanol intake, anxiety, reward and ethanol withdrawal. My ultimate goal is to validate a DOR-subtype as a new target for intervention in alcohol abuse and determine the properties of the most ideal DOR-subtype selective drug as a preclinical lead.

项目总结/文摘

项目成果

Delta Opioid Pharmacology in Relation to Alcohol Behaviors.

• DOI: 10.1007/164_2016_30
• 发表时间: 2018
• 期刊: Handbook of experimental pharmacology
• 作者: Alongkronrusmee, Doungkamol;Chiang, Terrance;van Rijn, Richard M
• 通讯作者: van Rijn, Richard M

An integrated perspective on diabetic, alcoholic, and drug-induced neuropathy, etiology, and treatment in the US.

对美国糖尿病、酒精和药物引起的神经病变、病因和治疗的综合视角。

• DOI: 10.2147/jpr.s125987
• 发表时间: 2017
• 期刊: Journal of pain research
• 影响因子: 2.7
• 作者: Zeng,Lily;Alongkronrusmee,Doungkamol;vanRijn,RichardM
• 通讯作者: vanRijn,RichardM

Involvement of delta opioid receptors in alcohol withdrawal-induced mechanical allodynia in male C57BL/6 mice.

• DOI: 10.1016/j.drugalcdep.2016.08.017
• 发表时间: 2016-10-01
• 期刊: Drug and alcohol dependence
• 影响因子: 4.2
• 作者: Alongkronrusmee D;Chiang T;van Rijn RM
• 通讯作者: van Rijn RM