Date Approved

6-25-2019

Embargo Period

8-6-2019

Document Type

Thesis

Degree Name

M.S. Pharmaceutical Sciences

Department

Chemistry & Biochemistry

College

College of Science & Mathematics

First Advisor

Keck, Thomas M.

Second Advisor

Caputo, Gregory

Third Advisor

Wu, Chun

Subject(s)

Drug addiction--Treatment

Disciplines

Pharmacy and Pharmaceutical Sciences

Abstract

Drug addiction and abuse especially opiate and psychostimulant abuse is a national and global crisis. IBNtxA (3-iodobenzoyl naltrexamine) is a novel mu opioid receptor (MOR) agonist, a naloxone derivative, structurally related to the classical MOR antagonist naltrexone. Recent studies suggest IBNtxA preferentially signals through truncated MOR splice variants, producing a unique pharmacological profile resulting in potent analgesia with reduced side effects. It has been found that M. vaccae has immunoregulatory effects that can prevent stress-induced exaggeration of neuroinflammation in the brain. The purpose of our pilot study is to develop medication for addiction and neuropsychiatric disorders. According to our purpose, we evaluated a range of IBNtxA doses to more fully assess its abuse liability and antiaddiction properties and the preimmunization effect of heat-killed M. vaccae on cocaine addiction. IBNtxA represents an intriguing lead compound for preclinical drug development specifically targeting MOR splice variants, potentially creating effective analgesics with reduced side effects. Furthermore, IBNtxA could have use as an adjunct therapy in agonist replacement strategies (e.g., methadone). M. vaccae might be helpful for cocaine relapse. Current collaborative efforts are aimed to find the total signaling pathways of IBNtxA and the effect of M. vaccae on cocaine self-administration, cocaine induced neuroinflammations and to keep finding medicine for neurological diseases.

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