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

抑郁症仍然是每年超过1000万美国人的一种严重疾病。对于很大一部分人来说，现有的治疗选择失败了，而且这些人目前没有其他选择。最近，镇静/麻醉剂氯胺酮被发现对难治性抑郁症具有活性。然而，在实现它作为一种有效的治疗选择方面仍然存在问题，包括它的成瘾潜力和精神分裂特性。与NIMH和马里兰大学的研究人员合作，我们正在探索一种自然产生的氯胺酮代谢物是其抗抑郁活性的制剂的可能性。在一系列研究中，这种关键代谢物概括了氯胺酮与抑郁症相关的所有表型，没有上瘾或精神分裂的影响。目前正在努力建立这种制剂的药物形式，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.