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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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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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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...
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In cases of acute poisoning, the primary objective is to prevent further absorption of the toxic substance into the body. Immediate interventions using various decontamination techniques targeting the gastrointestinal (GI) tract can achieve this. Decontamination is crucial to prevent poison from entering the systemic circulation, which involves washing affected areas with water and mild soap and removing contaminated clothing. Once external decontamination is done, attention must be turned to...
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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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Countermeasures for Preventing and Treating Opioid Overdose.

Charles P France1, Gerard P Ahern2, Saadyah Averick3

  • 1Department of Pharmacology, Addiction Research, Treatment and Training Center of Excellence, University of Texas Health Science Center, San Antonio, Texas, USA.

Clinical Pharmacology and Therapeutics
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New strategies are being explored to combat opioid overdose, addressing limitations of current treatments like naloxone (Narcan). Research focuses on novel antagonists and advanced delivery systems for potential use against synthetic opioid threats and opioid use disorder.

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Area of Science:

  • Pharmacology
  • Toxicology
  • Countermeasure Development

Background:

  • Naloxone, the primary opioid overdose medication, was approved by the FDA 50 years ago.
  • Naloxone's properties limit its effectiveness in mass casualty events involving weaponized synthetic opioids.
  • Existing medical countermeasures for opioid toxicity require enhancement to address emerging threats.

Purpose of the Study:

  • To explore emerging alternative approaches for treating opioid overdose.
  • To address the shortcomings of current medical countermeasures for opioid toxicity.
  • To investigate potential treatments for mass casualty events involving weaponized synthetic opioids.

Main Methods:

  • A trans-agency scientific meeting convened by NIAID/NIH in August 2019.
  • Presentations discussed novel opioid receptor antagonists and advanced therapeutic strategies.
  • Collaborative effort involving NIH, FDA, DTRA, and BARDA.

Main Results:

  • Intranasal nalmefene: longer-acting opioid receptor antagonist.
  • Methocinnamox: a novel opioid receptor antagonist.
  • Covalent naloxone nanoparticles, serotonin agonists, fentanyl-binding scaffolds, nanosponge decoy receptors, and antibody-based strategies were discussed.
  • These approaches may also treat opioid use disorder.

Conclusions:

  • Emerging approaches offer potential improvements over current opioid overdose treatments.
  • Novel strategies are crucial for addressing large-scale synthetic opioid threats.
  • These advancements could also benefit individuals with opioid use disorder.