title: Antagonists of the kappa opioid receptor.
abstract: The research community has increasingly focused on the development of OPRK antagonists as pharmacotherapies for the treatment of depression, anxiety, addictive disorders and other psychiatric conditions produced or exacerbated by stress. Short-acting OPRK antagonists have been recently developed as a potential improvement over long-acting prototypic ligands including nor-BNI and JDTic. Remarkably the short-acting LY2456302 is undergoing phase II clinical trials for the augmentation of the antidepressant therapy in treatment-resistant depression. This Letter reviews relevant chemical and pharmacological advances in the identification and development of OPRK antagonists.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, United States.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Urbano
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, United States.
authors.forename: Miguel
authors.initials: M
authors.lastname: Guerrero
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, United States; The Scripps Research Institute Molecular Screening Center, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, United States; Department of Immunology, The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, United States.
authors.forename: Hugh
authors.initials: H
authors.lastname: Rosen
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, United States. Electronic address: eroberts@scripps.edu.
authors.forename: Edward
authors.initials: E
authors.lastname: Roberts
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy; D003863:Depression / Q000188:drug therapy; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D008024:Ligands; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*; D013315:Stress, Psychological / Q000188:drug therapy; D019966:Substance-Related Disorders / Q000188:drug therapy
chemical_list: D008024:Ligands; D017473:Receptors, Opioid, kappa
keywords: Addictive disorders; Depression; OPRK antagonists; Short-acting; Stress-related disorders