PILOT--PRECLINICAL SAFETY STUDIES FOR INTRATHECAL DPDPE

基于临床前工作的充分证据表明 脊髓三角洲阿片受体可改变脑内神经递质 伤害性信息。数据量适中，但质量不佳 选择性的三角洲激动剂已经证实了这种可能性 人类。高选择性血管紧张素转换酶激动剂的研究进展 Delta受体增加了最终确认 脊髓三角洲受体在人类中的作用。因此，化合物 DPDPE就是这样一种制剂，并对其在人体内的作用进行了评估 脊椎分娩后将是一个重要的理论和 临床相关进展。本研究的目的是为了 大鼠和狗鞘内注射DPDPE的安全性 模特们。大鼠模型中的现有数据提供了初步的 确认DPDPE的安全性。之前的下一步 转移到人类身上是为了进一步表征DPDPE的安全性 在评估其在人体上的作用之前。具体地说， 目前的研究将I)确定脊髓DPDPE对 大鼠的脊髓血流；以及ii)定义 28天脊髓注射赋形剂的毒理学/组织病理学 或在定义明确的狗模型中注射两剂DEPDPE 长期放置的鞘内导管。基于广泛的 这些模型的体验，应该展示给狗狗模型吗 安全性，那么在以后考虑 用于检查脊柱的人体研究方案的发展 这种Delta型选择性激动剂的作用。

there is ample evidence based on preclinical work indicating that spinal delta opioid receptors can modify the processing of nociceptive information. Modest amounts of data with poorly selective delta agonists have confirmed this possibility in humans. The development of highly selective agonists for the delta receptor raises the possibility of finally confirming the role of spinal delta receptors in humans. Thus, the compound DPDPE is such an agent and assessment of its actions in humans after spinal delivery would be an important theoretical and clinically relevant advance. The present studies are aimed at defining the safety of DPDPE given intrathecally in rat and dog models. Existing data in a rat model has provided an initial confirmation of the safety of DPDPE. The next step prior to moving to humans is to further characterize the safety of DPDPE prior to assessing its action in humans. Specifically, the present studies will I) Define the effects of spinal DPDPE on spinal blood flow in the rat; and ii) Define the toxicology/histopathology of 28 day spinal infusion of vehicle or two doses of DEPDPE in a well defined dog model with chronically placed intrathecal catheters. Based on the extensive experience with these models, should the dog model display safety, it would be appropriate to subsequently consider the development of human studies protocols for examining the spinal effects of this delta selective agonist.