Combined Interactions with I₁-, I₂-Imidazoline Binding Sites and α₂-Adrenoceptors To Manage Opioid Addiction.

ABSTRACT: Tolerance and dependence associated with chronic opioid exposure result from molecular, cellular, and neural network adaptations. Such adaptations concern opioid and nonopioid systems, including α₂-adrenoceptors (α₂-ARs) and I₁- and I₂-imidazoline binding sites (IBS). Agmatine, one of the hypothesized endogenous ligands of IBS, targeting several systems including α₂-ARs and IBS, proved to be able to regulate opioid-induced analgesia and to attenuate the development of tolerance and dependence. Interested in the complex pharmacological profile of agmatine and considering the nature of its targets, we evaluated two series of imidazolines, rationally designed to simultaneously interact with I₁-/I₂-IBS or I₁

SUBMITTER: Giusepponi ME 

PROVIDER: S-EPMC5066154 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature