Fentanyl Molecule

Ball and Stick Model for Cannabidiol Molecule

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

Overview

Fentanyl was first synthesized by Paul Janssen in 1959 and was approved for medical use in the United States in 1968. As of 2017, fentanyl is one of the most widely used synthetic opioid in medicine.

Fentanyl is a potent synthetic opioid, which, ia similar to morphine. It produces a decrease in pain similar to morphine but is 50-100 times more potent.

It was introduced into medical practice as an intravenous anesthetic under the trade name of Sublimaze in the 1960s. prescriptions dispensed for fentanyl were approximately 6.5 million in 2015, 5.0 million in 2017, 3.2 million in 2019, 2.7 million in 2020, and 2.4 million in 2021.

Binding Site

How μ-Opioid Receptor Recognizes Fentanyl

abstract: "...The opioid crisis has escalated during the COVID-19 pandemic. More than half of the overdose-related deaths are related to synthetic opioids represented by fentanyl which is a potent agonist of mu-opioid receptor (mOR). In recent years, crystal structures of mOR complexed with morphine derivatives have been determined; however, structural basis of mOR activation by fentanyl-like synthetic opioids remains lacking. Exploiting the X-ray structure of mOR bound to a morphinan ligand and several state-of-the-art simulation techniques, including weighted ensemble and continuous constant pH molecular dynamics, we elucidated the detailed binding mechanism of fentanyl with mOR. Surprisingly, in addition to the orthosteric site common to morphinan opiates, fentanyl can move deeper and bind mOR through hydrogen bonding with a conserved histidine H297, which has been shown to modulate mOR’s ligand affinity and pH dependence in mutagenesis experiments, but its precise role remains unclear. .."

Molecular recognition of morphine and fentanyl by the human μ-opioid receptor

"...Morphine and fentanyl are among the most used opioid drugs that confer analgesia and unwanted side effects through both G protein and arrestin signaling pathways of μ-opioid receptor (μOR). Here, we report structures of the human μOR-G protein complexes bound to morphine and fentanyl, which uncover key differences in how they bind the receptor. We also report structures of μOR bound to TRV130, PZM21, and SR17018, which reveal preferential interactions of these agonists with TM3 side of the ligand-binding pocket rather than TM6/7 side. In contrast, morphine and fentanyl form dual interactions with both TM3 and TM6/7 regions. Mutations at the TM6/7 interface abolish arrestin recruitment of μOR promoted by morphine and fentanyl. Ligands designed to reduce TM6/7 interactions display preferential G protein signaling. Our results provide crucial insights into fentanyl recognition and signaling of μOR, which may facilitate rational design of next-generation analgesics. ..."

Dangers of Fentanyl Use

DEA Laboratory Testing Reveals that 6 out of 10 Fentanyl-Laced Fake Prescription Pills Now Contain a Potentially Lethal Dose of Fentanyl

"...WASHINGTON – The U.S. Drug Enforcement Administration is alerting the public of a sharp nationwide increase in the lethality of fentanyl-laced fake prescription pills. The DEA Laboratory has found that, of the fentanyl-laced fake prescription pills analyzed in 2022, six out of ten now contain a potentially lethal dose of fentanyl. This is an increase from DEA’s previous announcement in 2021 that four out of ten fentanyl-laced fake prescription pills were found to contain a potentially lethal dose. “More than half of the fentanyl-laced fake prescription pills being trafficked in communities across the country now contain a potentially deadly dose of fentanyl. This marks a dramatic increase – from four out of ten to six out of ten – in the number of pills that can kill,” said Administrator Anne Milgram. “These pills are being mass-produced by the Sinaloa Cartel and the Jalisco Cartel in Mexico. Never take a pill that wasn’t prescribed directly to you. Never take a pill from a friend. Never take a pill bought on social media. Just one pill is dangerous and one pill can kill.”

Laboratory testing indicates 7 out of every 10 pills seized by DEA contain a lethal dose of fentanyl. 2024

Graph below shows increase of seized fentanyl from 2017-2023

Even Worse than Fentanyl

Even Worse than Fentanyl

Benzimidazole opioids, also known as nitazenes

 

Nitazene molecule (PubChem)

Depending on the chemical formulation, some nitazenes are 800 times more potent than morphine and 40 times more than even fentanyl! They come in liquids, pills, and powder form. And just as illegal street drugs can be laced with fentanyl, they can also contain nitazenes without the user knowing. According to the CDC, a record ninety-two thousand people died of drug overdoses in 2020 and nearly two-thirds were from synthetic opioids, mostly from fentanyl. Up to 2,000 people may have died from nitazene since two thousand nineteen. The concern is that number will grow unless people are educated about the dangers they pose.

High-throughput quantification of emerging “nitazene” benzimidazole opioid analogs by microextraction and UHPLC–MS-MS

In 2019, the first nitazene was identified in the European drug market, and since then, 10 other analogs have followed. In the most recent European Monitoring Centre for Drugs and Drug Addiction report on new opioids, isotonitazene accounted for 22% of the seized material of new opioids (1). In Norway, three cases of nitazene overdoses have been confirmed in three different locations. Two of these cases had fatal outcomes (9, 10). Norwegian customs have also had four seizures of nitazenes (11).

There are several analogues in the nitazene family, with the potential for new ones to be developed. Some of those detected in illegal drug supplies include butonitazene, isotonitazene, protonitazene and metonitazene. Etonitazene has been reported to be the most potent​[4]​.Feb 8, 2024

Everything you need to know about nitazenes

 

In fiscal year 2023, U.S. Customs and Border Protection (CBP) seized 240,000 pounds of drugs at the southwest land border, which included an estimated 1.1 billion doses of fentanyl.