Developing a Peripherally-Acting Peptidic Galanin Analog for Treatment of Postoperative Pain

DESCRIPTION provided by applicant The development of non opioid analgesics for the control of postsurgical pain is widely acknowledged as an important goal The side effects of opioids most notably respiratory depression but also including sedation nausea constipation and sleep impairment make their use challenging and even potentially life threatening Of course the difficulties posed by opioid use are magnified tremendously by the potential for addiction and abuse In large part because of the need to limit the use of opioids the moderate severe or extreme pain experienced by about of patients after surgery is often undertreated Adjuvant agents such as gabapentin magnesium and ketamine are used in the perioperative setting andquot multimodal therapyandquot to reduce acute postoperative pain and the development of persistent pain as well as to reduce use of opioids Unfortunately however many of the most efficacious andquot add onandquot therapies also carry negative side effects related to the central nervous system CNS There remains a need for new classes of potent and effective analgesics for treatment of postoperative pain that do not have CNS related side effects and high abuse potential We believe that metabolically stable peripherally restricted galanin analogs have the potential to replace or reduce the use of opioids in treatment of acute postoperative pain However there is confusion in literature about the galanin receptor subtype that would be more effective in mediating antinociception We will evaluate two analogs in this proposal with the goal of selecting a lead candidate for phase efforts focused on drug development activities One of these analogs is somewhat selective for the galanin type receptor the other being somewhat galanin type receptor preferring Both have shown good efficacy in various rodent models of pain and no evidence of major side effects like those associated with opioids In this phase application we will evaluate our two analogs in mice to determine pharmacokinetic PK parameters potency and efficacy in the plantar incision model of postsurgical pain and toxicity over the course of a day study Completion of these aims will allow us to better define the PK efficacy and short term toxicity of our two analogs allowing us to select one compound as the lead for subsequent phase studies This phase project is the starting point for exploring the efficacy of galanin analogs for multiple pain states information gained in this project will supplement efforts to develop a galanin analog for other forms of pain beyond postoperative Metabolically stable peripherally restricted galanin analogs represent novel first in class pharmacologic therapies to replace or reduce use of opioids and other CNS active therapies in treatment of postoperative pain PUBLIC HEALTH RELEVANCE The development of non opioid analgesics for the control of postsurgical pain is widely acknowledged as an important goal Side effects of opioids include respiratory depression sedation nausea constipation sleep impairment and a high potential for abuse and addiction Navigen is developing novel metabolically stable peripherally restricted galanin analogs to replace or reduce the use of opioids in treatment of postoperative pain