Related Experiment Video
Updated: May 14, 2026
09:09
Preparation and Delivery of Protein Microcrystals in Lipidic Cubic Phase for Serial Femtosecond Crystallography
Published on: September 20, 2016
Development of κ opioid receptor antagonists
F Ivy Carroll1, William A Carlezon
1Center for Organic and Medicinal Chemistry, Research Triangle Institute , P.O. Box 12194, Research Triangle Park, North Carolina 27709, USA. fic@rti.org
Journal of Medicinal Chemistry
|January 31, 2013
Summary
Selective kappa opioid receptor (KOR) antagonists show promise for treating neuropsychiatric disorders. Preclinical and clinical research suggests KOR antagonists may counteract depression and drug-seeking behaviors.
Area of Science:
- Neuropharmacology
- GPCR signaling
Background:
- Kappa opioid receptors (KORs) are G-protein-coupled receptors (GPCRs) activated by dynorphin (DYN).
- High KOR expression in brain regions controlling emotion, motivation, and cognition.
- Chronic KOR activation in animal models is linked to depression, drug-seeking, and craving.
Purpose of the Study:
- To review preclinical development of selective KOR antagonists.
- To summarize existing clinical studies of KOR antagonists.
- To recommend future research directions for KOR antagonists in neuropsychiatric disorders.
Main Methods:
- Review of preclinical research on various selective KOR antagonist classes.
- Summary of clinical trial data for KOR antagonists.
- Analysis of research gaps and future work needed.
Main Results:
- Several classes of selective KOR antagonists have been developed preclinically.
- Clinical studies have been initiated to evaluate KOR antagonists.
- The therapeutic potential of KOR antagonists for neuropsychiatric conditions is under investigation.
Conclusions:
- Selective KOR antagonists are being developed as potential pharmacotherapies.
- Further research is required to establish the efficacy and safety of KOR antagonists for neuropsychiatric illnesses.
- KOR antagonists may offer a novel therapeutic strategy for stress-related disorders.
Related Concept Videos
01:22Opioid Receptors: Overview
Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2, D-Pen5]-enkephalin or DPDPE for...
01:25Analgesia and Pain Management
Pain is critical to various clinical pathologies, provoking an urgent need for effective management. Pain, whether acute or chronic, is a complex neurochemical process. Its alleviation depends on the type, with nonopioid analgesics effective for mild to moderate pain, such as musculoskeletal or inflammatory pain, while neuropathic pain responds best to anticonvulsants, tricyclic antidepressants, or serotonin/norepinephrine reuptake inhibitors. For severe acute or chronic pain, opioids may be...
01:28Drug-Receptor Interaction: Antagonist
An antagonist is a drug that binds strongly to a receptor without activating it. An antagonist prevents other molecules, such as neurotransmitters or hormones, from binding to the receptor and triggering a cellular response. Such interaction effectively hinders the normal physiological processes mediated by the receptor, resulting in various pharmacological effects depending on the specific receptor targeted.
Antagonists can be classified as competitive or noncompetitive based on their...
Antagonists can be classified as competitive or noncompetitive based on their...
01:15Opioid Analgesics: Synthetic and Semisynthetic Opioids
Synthetic and semisynthetic opioids are pivotal in pain management and tackling opioid addiction. Semisynthetic opioids, including morphinans (morphine derivatives), oxycodone, oxymorphone, hydrocodone, and hydromorphone, have improved pharmacokinetic profiles compared to morphine. Additionally, heroin and 6-MAM (6-Monoacetylmorphine) show better CNS penetration than morphine due to heightened lipid solubility. Hydromorphone, a potent opioid, undergoes hepatic metabolism to form the active...
01:25Drug-Receptor Interaction: Agonist
Agonists are drugs that interact with specific receptors in the body to produce a biological response. When an agonist binds to a receptor, it activates or enhances the receptor's function, leading to physiological effects. The interaction between agonist drugs and receptors is crucial for their therapeutic action in various medical treatments.
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous ligand's action.
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous ligand's action.
01:20Opioid Analgesics: Morphine and Other Natural Cogeners
Opioids are a class of drugs that mimic endogenous opioid peptides and act on opioid receptors, and help in pain relief. These compounds are classified as natural, synthetic, or semi-synthetic. Natural opioids, like morphine, codeine, and thebaine, are derived from the opium poppy plant (Papaver somniferum or Papaver album) and are termed opiates. Synthetic opioids are artificial, while semi-synthetic opioids combine natural and synthetic compounds. Morphine, a prototypical opioid, possesses a...