Opioids and opioid receptors; understanding pharmacological mechanisms as a key to therapeutic advances and mitigation of the misuse crisis
Opioids are a mainstay in acute pain management and produce their effects and side effects (e.g., tolerance, opioid-use disorder and immune suppression) by interaction with opioid receptors. I will discuss opioid pharmacology in some controversial areas of enquiry of anaesthetic relevance. The main...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | BJA Open |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772609623000205 |
| _version_ | 1797797916797042688 |
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| author | David G. Lambert |
| author_facet | David G. Lambert |
| author_sort | David G. Lambert |
| collection | DOAJ |
| description | Opioids are a mainstay in acute pain management and produce their effects and side effects (e.g., tolerance, opioid-use disorder and immune suppression) by interaction with opioid receptors. I will discuss opioid pharmacology in some controversial areas of enquiry of anaesthetic relevance. The main opioid target is the µ (mu,MOP) receptor but other members of the opioid receptor family, δ (delta; DOP) and κ (kappa; KOP) opioid receptors also produce analgesic actions. These are naloxone-sensitive. There is important clinical development relating to the Nociceptin/Orphanin FQ (NOP) receptor, an opioid receptor that is not naloxone-sensitive. Better understanding of the drivers for opioid effects and side effects may facilitate separation of side effects and production of safer drugs. Opioids bind to the receptor orthosteric site to produce their effects and can engage monomer or homo-, heterodimer receptors. Some ligands can drive one intracellular pathway over another. This is the basis of biased agonism (or functional selectivity). Opioid actions at the orthosteric site can be modulated allosterically and positive allosteric modulators that enhance opioid action are in development. As well as targeting ligand-receptor interaction and transduction, modulating receptor expression and hence function is also tractable. There is evidence for epigenetic associations with different types of pain and also substance misuse. As long as the opioid narrative is defined by the ‘opioid crisis’ the drive to remove them could gather pace. This will deny use where they are effective, and access to morphine for pain relief in low income countries. |
| first_indexed | 2024-03-13T03:55:29Z |
| format | Article |
| id | doaj.art-04af500ec2944e7489531c54fff9b776 |
| institution | Directory Open Access Journal |
| issn | 2772-6096 |
| language | English |
| last_indexed | 2024-03-13T03:55:29Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | BJA Open |
| spelling | doaj.art-04af500ec2944e7489531c54fff9b7762023-06-22T05:06:04ZengElsevierBJA Open2772-60962023-06-016100141Opioids and opioid receptors; understanding pharmacological mechanisms as a key to therapeutic advances and mitigation of the misuse crisisDavid G. Lambert0University of Leicester, Leicester, UKOpioids are a mainstay in acute pain management and produce their effects and side effects (e.g., tolerance, opioid-use disorder and immune suppression) by interaction with opioid receptors. I will discuss opioid pharmacology in some controversial areas of enquiry of anaesthetic relevance. The main opioid target is the µ (mu,MOP) receptor but other members of the opioid receptor family, δ (delta; DOP) and κ (kappa; KOP) opioid receptors also produce analgesic actions. These are naloxone-sensitive. There is important clinical development relating to the Nociceptin/Orphanin FQ (NOP) receptor, an opioid receptor that is not naloxone-sensitive. Better understanding of the drivers for opioid effects and side effects may facilitate separation of side effects and production of safer drugs. Opioids bind to the receptor orthosteric site to produce their effects and can engage monomer or homo-, heterodimer receptors. Some ligands can drive one intracellular pathway over another. This is the basis of biased agonism (or functional selectivity). Opioid actions at the orthosteric site can be modulated allosterically and positive allosteric modulators that enhance opioid action are in development. As well as targeting ligand-receptor interaction and transduction, modulating receptor expression and hence function is also tractable. There is evidence for epigenetic associations with different types of pain and also substance misuse. As long as the opioid narrative is defined by the ‘opioid crisis’ the drive to remove them could gather pace. This will deny use where they are effective, and access to morphine for pain relief in low income countries.http://www.sciencedirect.com/science/article/pii/S2772609623000205epigeneticsligand receptor interactionopioid receptorsopioidsopioids and immune functionopioids and vascular |
| spellingShingle | David G. Lambert Opioids and opioid receptors; understanding pharmacological mechanisms as a key to therapeutic advances and mitigation of the misuse crisis BJA Open epigenetics ligand receptor interaction opioid receptors opioids opioids and immune function opioids and vascular |
| title | Opioids and opioid receptors; understanding pharmacological mechanisms as a key to therapeutic advances and mitigation of the misuse crisis |
| title_full | Opioids and opioid receptors; understanding pharmacological mechanisms as a key to therapeutic advances and mitigation of the misuse crisis |
| title_fullStr | Opioids and opioid receptors; understanding pharmacological mechanisms as a key to therapeutic advances and mitigation of the misuse crisis |
| title_full_unstemmed | Opioids and opioid receptors; understanding pharmacological mechanisms as a key to therapeutic advances and mitigation of the misuse crisis |
| title_short | Opioids and opioid receptors; understanding pharmacological mechanisms as a key to therapeutic advances and mitigation of the misuse crisis |
| title_sort | opioids and opioid receptors understanding pharmacological mechanisms as a key to therapeutic advances and mitigation of the misuse crisis |
| topic | epigenetics ligand receptor interaction opioid receptors opioids opioids and immune function opioids and vascular |
| url | http://www.sciencedirect.com/science/article/pii/S2772609623000205 |
| work_keys_str_mv | AT davidglambert opioidsandopioidreceptorsunderstandingpharmacologicalmechanismsasakeytotherapeuticadvancesandmitigationofthemisusecrisis |