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Related Concept Videos

Opioid Receptors: Overview01:22

Opioid Receptors: Overview

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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,...
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Opioid Analgesics: Synthetic and Semisynthetic Opioids01:15

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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...
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Internal Receptors01:31

Internal Receptors

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Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.
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Opioid Analgesics: Morphine and Other Natural Cogeners01:20

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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...
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Drugs Affecting GI Tract Motility: Opioids as Antidiarrheal Agents01:17

Drugs Affecting GI Tract Motility: Opioids as Antidiarrheal Agents

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Diarrhea, a condition marked by frequent loose or watery bowel movements, can be triggered by multiple factors such as viral or bacterial infections, food intolerances, anxiety, medications, and digestive disorders. Symptoms may include abdominal pain, bloating, nausea, and cramping. Severe or prolonged diarrhea can lead to complications like electrolyte imbalances, malnutrition, and dehydration if left untreated.
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Protein Complexes with Interchangeable Parts01:57

Protein Complexes with Interchangeable Parts

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Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
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Updated: Feb 4, 2026

Biochemical Reconstitution of Steroid Receptor•Hsp90 Protein Complexes and Reactivation of Ligand Binding
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Untangling the complexity of opioid receptor function.

Rita J Valentino1, Nora D Volkow2

  • 1The National Institute on Drug Abuse, Bethesda, MD, 20892, USA. valentinorj@nida.nih.gov.

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
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Developing safer opioids requires understanding complex mu-opioid receptor (MOR) signaling. New tools reveal intricate receptor functions, paving the way for non-addictive analgesics and solutions to tolerance and dependence.

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Area of Science:

  • Pharmacology
  • Neuroscience
  • Molecular Biology

Background:

  • Mu-opioid receptor (MOR) agonists are potent analgesics but highly addictive, driving the search for safer alternatives.
  • Despite decades of research on endogenous opioid systems, non-addictive opioid analgesics remain elusive.
  • The opioid crisis necessitates innovative approaches to developing effective pain relief without addiction.

Purpose of the Study:

  • To review recent chemical and pharmacological findings on opioid receptor function.
  • To highlight how new molecular, genetic, and computational tools advance understanding of opioid receptors.
  • To explore new perspectives for developing safer and more effective opioid analgesics.

Main Methods:

  • Utilizing advanced molecular, genetic, and computational tools to study opioid receptors.
  • Elucidating structural dynamics, intracellular signaling, and cellular trafficking of opioid receptors.
  • Analyzing ligand-directed biased signaling and allosteric modulation of ligand interactions.

Main Results:

  • Opioid receptor function is complex, involving spatiotemporal signaling specificity.
  • Heterodimerization of opioid receptors and splice variants with distinct ligand specificities were identified.
  • New insights into ligand interactions and receptor modulation were revealed.

Conclusions:

  • Understanding the multi-layered complexity of opioid receptor function is crucial.
  • Basic research in opioid receptor chemistry and pharmacology guides the development of safer opioids.
  • Deciphering tolerance and physical dependence mechanisms is key to creating effective, non-addictive analgesics.