Medications for the Treatment of Alcohol Abuse and Dependence and Relapse

描述（由申请人提供）：酒精使用障碍（酒精滥用和酒精依赖）是世界范围内最普遍的精神障碍之一，并与大量的个人和社会成本相关。急性和慢性饮酒均已被证明会使个体面临健康问题的风险，包括酒精依赖，增加神经系统疾病、心血管疾病、癌症和肝损伤的风险。Lohocla研究公司通过合理的设计开发了一种新颖的、受专利保护的新化学实体，其首字母缩写为DCUKA。DCUKA同时针对影响酒精摄入的两个神经化学过程。我们的临床前研究表明，DCUKA减少酒精戒断过度兴奋，具有神经保护作用，减少焦虑，减少复发性饮酒，并减少总体酒精摄入量。Lohocla打算将DCUKA定位为不仅用于治疗酒精依赖（就像目前的治疗方法一样），而且还用于那些饮酒处于危险/有害水平并希望将其降低到更安全水平的个人。为了让Lohocla开始在人体中测试DCUKA，必须完成FDA要求的特定药代动力学和毒理学临床前研究。本申请资助期间将完成以下研究：（1）进一步确定DCUKA在非依赖动物中减少酒精摄入量的有效性;（2）开发基于质谱检测的灵敏测定方法，用于测定血液和组织中的DCUKA;（3）确定DCUKA在肝微粒体中的体内口服药代动力学和体外代谢;和（4）大鼠毒理学和安全性研究（急性和多次剂量耐受性、遗传毒性、慢性毒性、急性CNS安全性）。这些研究的完成将允许Lohocla研究提交探索性IND，从而将DCUKA定位为IND申请。

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.