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.
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