Medications for the Treatment of Alcohol Abuse and Dependence and Relapse

治疗酒精滥用、酒精依赖和复发的药物

基本信息

批准号：
7424025
负责人：
LAWRENCE DOUGLAS SNELL
金额：
$ 54.99万
依托单位：
LOHOCLA RESEARCH CORPORATION
依托单位国家：
美国
项目类别：
财政年份：
1995
资助国家：
美国
起止时间：
1995-07-01 至 2011-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7424025
关键词：
Abstinence Acute Address Affective Agonist Alcohol Withdrawal Seizures Alcohol abuse Alcohol consumption Alcohol dependence Alcohol withdrawal syndrome Alcohols Animal Model Animals Anti-Anxiety Agents Anticonvulsants Anxiety Area Arousal Biological Assay Biological Markers Blood Bone Marrow Books Brain Campral Carbamazepine Cardiovascular Diseases Chemicals Chromosome abnormality Chronic Clinical Clinical Research Clinical Trials Convulsions Data Detection Development Diagnosis Disease Disulfiram Dose Drug Kinetics Early treatment Effectiveness Esters Ethanol Feedback Funding Genetic Glutamate Receptor Glycine Grant Habits Half-Life Health Human In Vitro Individual Injury Intervention Intravenous Investigation Kinetics Legal patent Literature Liver Microsomes Maintenance Malignant neoplasm of liver Marketing Mass Spectrum Analysis Mental disorders Metabolism Micronucleus Tests Modeling Monoamine Oxidase Motor Mutation N-Methyl-D-Aspartate Receptors N-Methylaspartate Naltrexone Neuraxis Oral Oral Administration Patients Pharmaceutical Preparations Pharmacological Treatment Pharmacology Pharmacotherapy Phenytoin Plasma Population Positioning Attribute Prevention Primary Care Physician Process Prodrugs Psychotherapy Range Rattus Recovery Relapse Research Risk Safety Self Administration Services Site Sleeplessness Sodium Channel Specificity Sprague-Dawley Rats Structure-Activity Relationship Testing Tissue Banks Tissues Toxic effect Toxicokinetics Toxicology Treatment Efficacy Tremor United States United States Food and Drug Administration Week Withdrawal Withdrawal Symptom acamprosate alcohol abuse therapy alcohol effect alcohol preferring rats alcohol relapse alcohol use disorder base carbohydrate-deficient transferrin chronic alcohol ingestion cost craving dependence relapse deprivation design diphenyl disability burden disorder later incidence prevention drinking in vivo inhibitor/antagonist interest liquid chromatography mass spectrometry mind control neurochemistry neuroregulation novel pharmacophore pre-clinical preclinical study problem drinker psychosocial quinoline relating to nervous system response voltage

项目摘要

DESCRIPTION (provided by applicant): Alcohol use disorders (alcohol abuse and alcohol dependency) are among the most prevalent mental disorders worldwide and and are associated with substantial personal and societal costs Both acute and chronic consumption of alcohol have been shown to place individuals at risk for health problems including alcohol dependence, increased risks for neural disorders, cardiovascular disease, cancers, and liver injury. Lohocla Research Corporation has developed, through rational design, a novel, patent-protected new chemical entity assigned the acronym DCUKA. DCUKA simultaneously targets two neurochemical processes influencing alcohol intake. Our preclinical studies demonstrate that DCUKA reduces alcohol withdrawal hyperexcitability, is neuroprotective, reduces anxiety, reduces relapse drinking and lessens overall alcohol intake. Lohocla intends to position DCUKA not just for the treatment of alcohol dependence (as current treatments do), but also for individuals who are drinking alcohol at hazardous/harmful levels and wish to reduce them to safer levels. In order for Lohocla to begin testing DCUKA in humans, specific FDA-required pharmacokinetic and toxicological preclinical investigations must be completed. The following studies will be accomplished during funding of this application: (1) Further establish the effectiveness of DCUKA in reducing alcohol intake in non-dependent animals; (2) Develop a sensitive assay based on mass spectrometry detection for assaying DCUKA in blood and tissues; (3) ascertain in vivo oral pharmacokinetics and in vitro metabolism of DCUKA in liver microsomes; and (4) toxicology and safety studies in rats (acute and multiple dose tolerance, genetic toxicity, chronic toxicity, acute CNS safety). Completion of these studies will allow Lohocla research to file for an exploratory IND and, thereby, position DCUKA for an IND application.

描述（由申请人提供）：酒精使用障碍（酒精滥用和酒精依赖）是全球最普遍的精神障碍之一，并且与急性和社会成本有关，急性和社会成本既急性和长期消费饮酒均已证明，可以使个人处于健康问题的风险，包括酒精疾病，包括神经障碍，心血管疾病，心血管疾病，Cancers，Cancers和Liver，Liver，Liver，Liver，Liver，Liver，Liver，Liver，Liver，Liver，Liver，Liver，Liver，Liver和Liver。 Lohocla Research Corporation通过理性设计开发了一个新颖的专利保护的新化学实体DCUKA。 DCUKA同时针对两个影响酒精摄入的神经化学过程。我们的临床前研究表明，DCUKA降低了酒精戒断过度兴奋性，具有神经保护性，减少焦虑，减少饮酒并减少整体酒精摄入量。洛霍克拉（Lohocla）打算将DCUKA定位不仅是为了治疗酒精依赖性（如当前的治疗方法），还适用于以有害/有害水平饮酒并希望将其降低到更安全的水平的人。为了使Lohocla开始在人类中测试DCUKA，必须完成特定的FDA款药代动力学和毒理学临床前研究。在此应用程序的资助期间将完成以下研究：（1）进一步确定DCUKA在减少非依赖动物中酒精摄入量的有效性；（2）基于质谱检测来开发一种敏感测定法，以测定血液和组织中的DCUKA；（3）确定肝微粒体中DCUKA的体内口服药代动力学和体外代谢；（4）大鼠的毒理学和安全研究（急性和多种剂量耐受性，遗传毒性，慢性毒性，急性中枢神经系统安全）。这些研究的完成将使Lohocla研究能够提交探索性IND，从而将DCUKA定位为IND应用。