Development of (R,R)-dehydronorketamine for treatment resistant depression

抑郁症仍然是一种严重的医疗疾病，每年有超过1000万美国人。对于很大一部分人来说，现有的治疗方案失败了，这些人目前没有选择。最近，镇静/麻醉剂氯胺酮已被发现在治疗难治性抑郁症中具有活性。然而，在实现其作为一种有效的治疗选择方面仍然存在问题，包括其成瘾潜力和拟精神病特性。与NIMH和马里兰州大学的研究人员合作，我们正在探索氯胺酮的天然代谢物是负责其抗癫痫活性的药物的潜力。在一系列研究中，这种关键代谢物概括了氯胺酮的所有抑郁相关表型，而没有成瘾或拟精神病作用。目前正在努力建立这种药物的药物形式，以启动临床试验。

Depression remains a serious medical illness for over 10 million Americans annually. For a large percentage, the existing treatment options fail, and there are no current options for these individuals. Recently, the sedative/anesthetic ketamine has been discovered to possess activity in treatment-resistant depression. There remain, however, issues in its realization as an effective therapeutic option, including its addictive potential and psychotomimetic properties. Working with researchers at NIMH and the University of Maryland, we are exploring the potential that a naturally occurring metabolite of ketamine is the agent responsible for its anti-depressant activity. In a cadre of studies this key metabolite recapitulates all depression-relative phenotypes of ketamine without the addictive or psychotomimetic effects. Efforts to establish a pharmaceutical form of this agent for initiation of a clinical trial are currently underway.