Preclinical assessment of the GluN2B inhibitor clinical candidate NP10679 as a medication to prevent opiate abuse relapse

Abstract The current status of opiate abuse in the US has been characterized as arapidly evolving publichealth crisisrequiring the need for new treatments to address the problemPersistent relapse toaddictive drug use is a significant challenge to addiction therapyMedications targeting theneurobiology underlying relapse offer additional avenues for treatmentGlutamate signaling iscritically involved in the dependence on addictive substancesChronic use of drugs of abuse suchas heroincocaine and nicotine induces long lasting changes in glutamate homeostasis that enhanceglutamate signaling in key brain areasInhibition of the GluN B subtype of NMDA receptors has beenproposed as a valid target for relapse preventionWe propose that NPa pH context dependentGluN B selective N methyl d aspartate receptorNMDARinhibitorcould provide benefit as atreatment to prevent relapse to opiate abuseIn this proposal we provide a rationale for targetingGluN B NMDA receptor inhibition for relapse prevention and present the profile of NPthat ledto its INDWe then propose experiments to further de risk the compound to ascertain if thecompound deserves further consideration for development in the area of opiate addiction The work described in this grant will facilitate the evaluation of the GluN B inhibitor NPanagent proposed as a therapeutic to ameliorate impairment subsequent to subarachnoid hemorrhageforuse as an intervention to prevent opiate abuse relapse