Opioid Analgesics and Opioid Antagonists

1980 ◽  
pp. 37-67
Author(s):  
Abraham Wikler
Keyword(s):  
Opioid Analgesics ◽  
Opioid Antagonists

scholarly journals Biased Opioid Antagonists as Modulators of Opioid Dependence: Opportunities to Improve Pain Therapy and Opioid Use Management

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4163 ◽  
Author(s):  
Wolfgang Sadee ◽  
John Oberdick ◽  
Zaijie Wang
Keyword(s):  
Opioid Dependence ◽  
Pain Therapy ◽  
Active Form ◽  
Opioid Analgesics ◽  
Opioid Antagonist ◽  
Opioid Antagonists ◽  
Opioid Use ◽  
Opioid Agonist ◽  
Opposing Effects

Opioid analgesics are effective pain therapeutics but they cause various adverse effects and addiction. For safer pain therapy, biased opioid agonists selectively target distinct μ opioid receptor (MOR) conformations, while the potential of biased opioid antagonists has been neglected. Agonists convert a dormant receptor form (MOR-μ) to a ligand-free active form (MOR-μ*), which mediates MOR signaling. Moreover, MOR-μ converts spontaneously to MOR-μ* (basal signaling). Persistent upregulation of MOR-μ* has been invoked as a hallmark of opioid dependence. Contrasting interactions with both MOR-μ and MOR-μ* can account for distinct pharmacological characteristics of inverse agonists (naltrexone), neutral antagonists (6β-naltrexol), and mixed opioid agonist-antagonists (buprenorphine). Upon binding to MOR-μ*, naltrexone but not 6β-naltrexol suppresses MOR-μ*signaling. Naltrexone blocks opioid analgesia non-competitively at MOR-μ*with high potency, whereas 6β-naltrexol must compete with agonists at MOR-μ, accounting for ~100-fold lower in vivo potency. Buprenorphine’s bell-shaped dose–response curve may also result from opposing effects on MOR-μ and MOR-μ*. In contrast, we find that 6β-naltrexol potently prevents dependence, below doses affecting analgesia or causing withdrawal, possibly binding to MOR conformations relevant to opioid dependence. We propose that 6β-naltrexol is a biased opioid antagonist modulating opioid dependence at low doses, opening novel avenues for opioid pain therapy and use management.

scholarly journals Opioids in the treatment of non-specific acute and chronic pain

Pain medicine ◽  
2019 ◽  
Vol 4 (1) ◽  
pp. 22-36
Author(s):  
D V Dmytriiev ◽  
O A Zaletska ◽  
D I Bortnik
Keyword(s):  
Chronic Pain ◽  
Opioid Analgesics ◽  
Opioid Therapy ◽  
Opioid Antagonists ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Opioid Prescription ◽  
Economic Problems ◽  
Partial Agonists ◽  
Prescription Form ◽  
Effective Use

After reading this article, the reader will be familiar with the general classes of opioid agonists and partial agonists, the basics of the pharmacokinetics and pharmacodynamics of opioids, the risks of opioid therapy and the requirements for the safe and effective use of opioids in acute and chronic pain. The use of opioids during surgical procedures or anesthesia is not discussed. Also, there is no discussion about various available opioid antagonists that are used to treat overdose and the various disorders associated with their use (including naloxone and naltrexone). Opioids are available, the most powerful and effective analgesics, and have become acceptable drugs for the treatment of acute and cancerous pain. However, there is concern about their use in case of chronic pain, if there is no cancer, because they are long-range ineffective but best suited for stopping this pain. Opioid prescription must be monitored for better use. Chronic pain creates discomfort for these patients, reducing their productivity and efficiency, which, in turn, can lead to economic problems in the country. The choice of Nalbuphine is due to the following reasons: the opioid, which is comparable to morphine by its analgesic potential, but has a better safety profile for nausea, vomiting and respiratory depression; not subject to strict quantitative accounting (extract on prescription form 1); the choice of opioid analgesics is significantly limited in Ukraine.

scholarly journals Biased Opioid Antagonists as Modulators of Opioid Dependence: Opportunities to Improve Pain Therapy and Opioid Use Management

2020 ◽  
Author(s):  
Wolfgang Sadee ◽  
John Oberdick ◽  
Zaijie Wang
Keyword(s):  
Opioid Dependence ◽  
Pain Therapy ◽  
Active Form ◽  
Opioid Analgesics ◽  
Opioid Antagonist ◽  
Opioid Antagonists ◽  
Opioid Use ◽  
Opioid Agonist ◽  
Opposing Effects

Opioid analgesics are effective pain therapeutics but cause various adverse effects and addiction. For safer pain therapy, biased opioid agonists selectively target distinct m opioid receptor (MOR) conformations, while the potential of biased opioid antagonists has been neglected. Agonists convert a dormant receptor form (MOR-m) to a ligand-free active form (MOR-m*), which mediates MOR signaling. Moreover, MOR-m converts spontaneously to MOR-m* (basal signaling). Persistent upregulation of MOR-m* has been invoked as a hallmark of opioid dependence. Contrasting interactions with both MOR-m and MOR-m* can account for distinct pharmacological characteristics of inverse agonists (naltrexone), neutral antagonists (6b-naltrexol), and mixed opioid agonist-antagonists (buprenorphine). Upon binding to MOR-m*, naltrexone but not 6b-naltrexol suppresses MOR-m*signaling. Naltrexone blocks opioid analgesia non-competitively at MOR-m*with high potency, whereas 6BN must compete with agonists at MOR-m, accounting for ~100-fold lower in vivo potency. Buprenorphine’s bell-shaped dose-response curve may also result from opposing effects on MOR-m and MOR-m*. In contrast, we find that 6b-naltrexol potently prevents dependence, below doses affecting analgesia or causing withdrawal, possibly binding to MOR conformations relevant to opioid dependence. We propose that 6b-naltrexol is a biased opioid antagonist modulating opioid dependence at low doses, opening novel avenues for opioid pain therapy and use management.

Abhängigkeitspotenzial und andere Risiken von Opioidanalgetika im Alter

2017 ◽  
Vol 63 (2) ◽  
pp. 99-114 ◽  
Author(s):  
Dirk K. Wolter
Keyword(s):  
Adverse Effects ◽  
Psychische Störungen ◽  
Opioid Analgesics ◽  
Alte Menschen ◽  
Dsm 5 ◽  
Icd 10

Zusammenfassung. Zielsetzung: Übersicht über Suchtpotenzial und andere Risiken von Opioidanalgetika im höheren Lebensalter. Methodik: Narrativ review. Literaturrecherche in PubMed (Suchbegriffe: opioid analgesics UND abuse; opioid analgesics UND dependence; opioid analgesics UND addiction; opioid analgesics UND adverse effects; jeweils UND elderly) sowie aktuellen einschlägigen Standardwerken; Auswahl nach altersmedizinischer Relevanz und Aktualität. Ergebnisse: Die Verordnung von Opioidanalgetika (OA) hat in den letzten 25 Jahren massiv zugenommen, die weitaus meisten Verordnungen entfallen auf alte Menschen und Menschen mit chronischen Nicht-Tumorschmerzen (CNTS). Die diagnostischen Kriterien für die Opiatabhängigkeit in ICD-10 und DSM-5 sind für die OA-Behandlung von CNTS ungeeignet. Bei langfristiger OA-Behandlung bei CNTS kann eine spezifische Form von Abhängigkeit entstehen, die nicht mit der illegalen Opiat-(Heroin-)Sucht gleichzusetzen ist. Vorbestehende Suchterkrankungen und andere psychische Störungen sind die wesentlichsten Risikofaktoren. Weitere Nebenwirkungen sind zu beachten. Schmerztherapie bei Suchtkranken stellt eine besondere Herausforderung dar. Schlussfolgerungen: Die Anwendung von OA bei CNTS verlangt eine sorgfältige Indikationsstellung. Die besondere Form der Abhängigkeit von OA ist nicht ausreichend erforscht und wird zu wenig beachtet.

Effect of Chemotherapy and Predictive Factors for Nausea or Vomiting in Patients with Cancer Receiving Opioid Analgesics for the First Time

2020 ◽  
Vol 15 (3) ◽  
pp. 213-220
Author(s):  
Masami Yamada ◽  
Chikako Matsumura ◽  
Yumi Jimaru ◽  
Rie Ueno ◽  
Sari Torii ◽  
...  
Keyword(s):  
Predictive Factors ◽  
Opioid Analgesics ◽  
Patients With Cancer ◽  
First Time

Sending out Biased Signals: an Appropriate Proposition for Pain?

2019 ◽  
Vol 32 (2) ◽  
pp. 108-110 ◽  
Author(s):  
E. Besserer-Offroy ◽  
P. Sarret
Keyword(s):  
Side Effects ◽  
Acute Pain ◽  
Gold Standard ◽  
Pain Treatment ◽  
Opioid Analgesics ◽  
Mu Opioid Receptor ◽  
Clinical Development ◽  
Mu Opioid ◽  
Development Stages ◽  
The Past

In the past few years, several biased ligands acting at the mu-opioid receptor were reported in the literature. These agonists are aimed at reducing pain while having fewer side effects than morphine, the gold standard of opioid analgesics. In this mini-review, we describe and discuss the recent advances in mu-biased ligands actually in preclinical and clinical development stages, including the latest U.S. Food and Drug Administration review of oliceridine, a biased mu-agonist for moderate to severe acute pain treatment developed by the company Trevena.

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