Abuse Liability and Anti‐Addiction Potential of the Atypical Mu Opioid Receptor Agonist IBNtxA

Abstract

OBJECTIVEIBNtxA is a novel μ opioid receptor (MOR) agonist, structurally related to the classical MOR antagonist naltrexone, that preferentially signals through truncated MOR splice variants. This unique pharmacological profile produces potent analgesia with reduced side effects, including no conditioned place preference (CPP) when tested at a single dose. The purpose of this study is to 1) evaluate a range of IBNtxA doses to more fully assess its abuse liability and 2) determine the effects of IBNtxA on morphine CPP expression and reinstatement of morphine CPP.METHODSIBNtxA was synthesized and compared to morphine in standard CPP expression assays. Following morphine CPP training, IBNtxA was tested for its effects in inducing CPP reinstatement on its own or attenuating morphine‐primed reinstatement.RESULTS and CONCLUSIONSIBNtxA is an intriguing preclinical drug that opens the door to new MOR splice variant‐selective pharmacotherapeutics with effective analgesic properties but reduced side effects. IBNtxA may have utility as an adjunct therapy in agonist replacement strategies (e.g., methadone). Current collaborative efforts are aimed at developing novel analogues of IBNtxA for further analysis and understanding ligand‐receptor interactions across MOR splice variants using molecular modeling.Support or Funding InformationRowan University Seed Fund; travel support from Dean of College of Science and Mathematics and the Rowan University Assistant Professor and Instructor Travel Fund.