Naloxone Molecule

Ball and Stick Model for Naloxone Molecule

To View the Naloxone Molecule in 3D --->>in 3D with Jsmol

Overview

Naloxone is a medicine that can treat a fentanyl overdose when given right away. It works by rapidly binding to opioid receptors and blocking the effects of opioid drugs. But fentanyl is stronger than other opioid drugs like morphine and might require multiple doses of naloxone.

Naloxone is an opioid antagonist medication used to block or reverse the effects of opioid drugs, particularly within the setting of drug overdoses which are rapidly becoming a leading cause of death worldwide. More specifically, naloxone has a high affinity for μ-opioid receptors, where it acts as an inverse agonist, causing the rapid removal of any other drugs bound to these receptors. --Pub Chem

Naloxone was patented in 1961 and approved for opioid overdose in the United States in 1971. It is on the World Health Organization's List of Essential Medicines.

Naloxone Chemical Structure

Chemical Formula C₁₉H₂₁NO₄

Binding Site

Mapping the naloxone binding sites on the mu-opioid receptor using cell-based photocrosslinkers-- 2016 source

"...Naloxone is an alkaloid antagonist that acts as an antidote to opioids through the mu-opioid receptor (MOR), a G protein-coupled receptor. However, its binding site on the MOR remains unknown... In conclusion, these results indicate that MOR has two naloxone binding sites and that the hydrophobic and polar/uncharged residues within these sites are important for naloxone binding. .."

Dynamic recognition of naloxone, morphine and endomorphin1 in the same pocket of µ-opioid receptors --2022 source

"...Morphine, the most widely used analgesic, relieves severe pain by activating the μ-opioid receptor (MOR), whereas naloxone, with only slight structural changes compared to morphine, exhibits inhibitory effect, and is used to treat opioid abuse...We verified the role of some key residues in the dynamic recognition of naloxone and morphine and identified the key residue I322, which leads to differential recognition of morphine and naloxone ..."

New compound could supercharge naloxone in fight against opioid overdoses

"...In a Stanford Medicine-led study, researchers combed through billions of compounds to find one that could enhance naloxone’s ability to fend off more potent opioids, with promising results in mice...."

https://med.stanford.edu/news/all-news/2024/07/naloxone-compound.html

"...The new compound belongs to an unusual class of drugs that don’t directly target the active site on receptors. Instead, they bind elsewhere on the receptor but trigger a structural change that alters the active site. Known as allosteric modulators they create new possibilities in drug development, but are trickier to identify,..

Evan O'Brien lead author (A µ-opioid receptor modulator that works cooperatively with naloxone --Nauture Journal) --

Naloxone binding to an opioid receptor turns it mostly off, but not all the way ---“Our data shows that compound 368 is able to increase the binding of naloxone and turn the receptor off more completely.”

What precautions are needed when giving naloxone?

"...Naloxone works to reverse opioid overdose in the body for only 30 to 90 minutes. But many opioids remain in the body longer than that. Because of this, it is possible for a person to still experience the effects of an overdose after a dose of naloxone wears off. Also, some opioids are stronger and might require multiple doses of naloxone. Therefore, one of the most important steps to take is to call 911 so the individual can receive immediate medical attention. NIDA is supporting research for stronger formulations for use with potent opioids like fentanyl.

People who are given naloxone should be observed constantly until emergency care arrives. They should be monitored for another 2 hours after the last dose of naloxone is given to make sure breathing does not slow or stop. Tolerance vs. Dependence vs. Addiction Long-term use of prescription opioids, even as prescribed by a doctor, can cause some people to develop a tolerance, which means that they need higher and/or more frequent doses of the drug to get the desired effects. Drug dependence occurs with repeated use, causing the neurons to adapt so they only function normally in the presence of the drug. The absence of the drug causes several physiological reactions, ranging from mild in the case of caffeine, to potentially life-threatening, such as with heroin. Some chronic pain patients are dependent on opioids and require medical support to stop taking the drug. Drug addiction is a chronic disease characterized by compulsive, or uncontrollable, drug seeking and use despite harmful consequences and long-lasting changes in the brain. The changes can result in harmful behaviors by those who misuse drugs, whether prescription or illicit drugs. ..

People with physical dependence on opioids may have withdrawal symptoms within minutes after they are given naloxone. .."

source: Naloxone DrugFacts -- NIH