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Biomolecules Sep 2022Despite various advantages, opioid peptides have been limited in their therapeutic uses due to the main drawbacks in metabolic stability, blood-brain barrier... (Review)
Review
Despite various advantages, opioid peptides have been limited in their therapeutic uses due to the main drawbacks in metabolic stability, blood-brain barrier permeability, and bioavailability. Therefore, extensive studies have focused on overcoming the problems and optimizing the therapeutic potential. Currently, numerous peptide-based drugs are being marketed thanks to new synthetic strategies for optimizing metabolism and alternative routes of administration. This tutorial review briefly introduces the history and role of natural opioid peptides and highlights the key findings on their structure-activity relationships for the opioid receptors. It discusses details on opioid peptidomimetics applied to develop therapeutic candidates for the treatment of pain from the pharmacological and structural points of view. The main focus is the current status of various mimetic tools and the successful applications summarized in tables and figures.
Topics: Analgesics, Opioid; Drug Discovery; Opioid Peptides; Peptidomimetics; Receptors, Opioid
PubMed: 36139079
DOI: 10.3390/biom12091241 -
Cleveland Clinic Journal of Medicine Jun 2016Older adults compose a large portion of patients with persistent pain. Opioid analgesics are widely used to treat acute and persistent pain in cancer and end-of-life... (Review)
Review
Older adults compose a large portion of patients with persistent pain. Opioid analgesics are widely used to treat acute and persistent pain in cancer and end-of-life care, but their use in other types of persistent pain in older adults is controversial. Clinicians and regulators must work together, balancing the legitimate medical need for opioids while acknowledging increasing opioid misuse and morbidity and mortality related to opioids.
Topics: Aged; Aged, 80 and over; Analgesics, Opioid; Chronic Pain; Female; Humans; Male; Pain Management; Prescription Drug Overuse
PubMed: 27281257
DOI: 10.3949/ccjm.83a.15023 -
The Neuroscientist : a Review Journal... Dec 2022Chronic pain represents one of the most serious worldwide medical problems, in terms of both social and economic costs, often causing severe and intractable physical and... (Review)
Review
Chronic pain represents one of the most serious worldwide medical problems, in terms of both social and economic costs, often causing severe and intractable physical and psychological suffering. The lack of biological markers for pain, which could assist in forming clearer diagnoses and prognoses, makes chronic pain therapy particularly arduous and sometimes harmful. Opioids are used worldwide to treat chronic pain conditions, but there is still an ambiguous and inadequate understanding about their therapeutic use, mostly because of their dual effect in acutely reducing pain and inducing, at the same time, tolerance, dependence, and a risk for opioid use disorder. In addition, clinical studies suggest that opioid treatment can be associated with a high risk of immune suppression and the development of inflammatory events, worsening the chronic pain status itself. While opioid peptides and receptors are expressed in both central and peripheral nervous cells, immune cells, and tissues, the role of opioids and their receptors, when and why they are activated endogenously and what their exact role is in chronic pain pathways is still poorly understood. Thus, in this review we aim to highlight the interplay between pain and immune system, focusing on opioids and their receptors.
Topics: Humans; Analgesics, Opioid; Chronic Pain; Immune System
PubMed: 34269117
DOI: 10.1177/10738584211030493 -
Revista de Investigacion Clinica;... 2023Synthetic opioids have played a significant role in the current opioid crisis in the United States (U.S.) and Canada and are a matter of concern worldwide. New... (Review)
Review
Synthetic opioids have played a significant role in the current opioid crisis in the United States (U.S.) and Canada and are a matter of concern worldwide. New psychoactive opioids (NPOs) are classified in the internationally recognized new psychoactive substances (NPSs) category. This group comprises compounds that may have been synthesized decades ago but appeared only recently in the illicit drug market. Such is the case of fentanyl, fentanyl analogs, and non-fentanyl opioids. Most NPOs have effects similar to morphine, including euphoria and analgesia, and can produce fatal respiratory depression. Here, we present an overview of the systemic and molecular effects of main NPOs, their classification, and their pharmacological properties. We first review the fentanyl group of NPOs, including the four compounds of clinical use (fentanyl, alfentanil, sufentanil, and remifentanil) and the veterinary drug carfentanil. We also provide essential information on non-medical fentanyl analogs and other synthetic opioids such as brorphine, etonitazene, and MT-45, used as adulterants in commonly misused drugs. This paper also summarizes the scarce literature on the use of NPOs in Mexico. It concludes with a brief review of the challenges to prevention and treatment posed by NPOs and some recommendations to face them.
Topics: Humans; United States; Analgesics, Opioid; Remifentanil; Canada; Mexico
PubMed: 37441771
DOI: 10.24875/RIC.23000109 -
Anaesthesia May 2019
Topics: Analgesics; Analgesics, Opioid; Anesthesia
PubMed: 30802930
DOI: 10.1111/anae.14611 -
Neuropharmacology Mar 2021Pain is a complex experience with far-reaching organismal influences ranging from biological factors to those that are psychological and social. Such influences can... (Review)
Review
Pain is a complex experience with far-reaching organismal influences ranging from biological factors to those that are psychological and social. Such influences can serve as pain-related risk factors that represent susceptibilities to opioid use disorder. This review evaluates various pain-related risk factors to form a consensus on those that facilitate opioid abuse. Epidemiological findings represent a high degree of co-occurrence between chronic pain and opioid use disorder that is, in part, driven by an increase in the availability of opioid analgesics and the diversion of their use in a non-medical context. Brain imaging studies in individuals with chronic pain that use/abuse opioids suggest abuse-related mechanisms that are rooted within mesocorticolimbic processing. Preclinical studies suggest that pain states have a limited impact on increasing the rewarding effects of opioids. Indeed, many findings indicate a reduction in the rewarding and reinforcing effects of opioids during pain states. An increase in opioid use may be facilitated by an increase in the availability of opioids and a decrease in access to non-opioid reinforcers that require mobility or social interaction. Moreover, chronic pain and substance abuse conditions are known to impair cognitive function, resulting in deficits in attention and decision making that may promote opioid abuse. A better understanding of pain-related risk factors can improve our knowledge in the development of OUD in persons with pain conditions and can help identify appropriate treatment strategies. This article is part of the special issue on 'Vulnerabilities to Substance Abuse.'.
Topics: Analgesics, Opioid; Animals; Chronic Pain; Conditioning, Psychological; Humans; Opioid-Related Disorders; Reinforcement, Psychology; Risk Factors
PubMed: 33524407
DOI: 10.1016/j.neuropharm.2021.108476 -
Molecular Psychiatry Apr 2019The United States is in the midst of an opioid addiction and overdose crisis precipitated and exacerbated by use of prescription opioid medicines. The majority of opioid... (Review)
Review
The United States is in the midst of an opioid addiction and overdose crisis precipitated and exacerbated by use of prescription opioid medicines. The majority of opioid prescriptions are dispensed to patients with comorbid mood disorders including major depressive disorder (MDD). A growing body of research indicates that the endogenous opioid system is directly involved in the regulation of mood and is dysregulated in MDD. This involvement of the endogenous opioid system may underlie the disproportionate use of opioids among patients with mood disorders. Emerging approaches to address endogenous opioid dysregulation in MDD may yield novel therapeutics that have a low or absent risk of abuse and addiction relative to µ-opioid agonists. Moreover, agents targeting the endogenous opioid system would be expected to yield clinical benefits qualitatively different from conventional monaminergic antidepressants. The development of safe and effective agents to treat MDD-associated endogenous opioid dysregulation may represent a distinct and currently underappreciated means of addressing treatment resistant depression with the potential to attenuate the on-going opioid crisis.
Topics: Analgesics, Opioid; Depression; Depressive Disorder, Major; Drug Overdose; Humans; Mood Disorders; Opioid-Related Disorders; Prescription Drugs; United States
PubMed: 29955162
DOI: 10.1038/s41380-018-0117-2 -
British Journal of Pharmacology Jan 2015This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit...
This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2
Topics: Allosteric Regulation; Analgesics, Opioid; Animals; Drug Tolerance; Humans; Neurons; Opioid-Related Disorders; Protein Multimerization; Receptors, Opioid, delta; Receptors, Opioid, mu
PubMed: 25537825
DOI: 10.1111/bph.13028 -
Current Opinion in Pharmacology Dec 2017The prevailing opioid crisis has necessitated the need to understand mechanisms leading to addiction and tolerance, the major contributors to overdose and death and to... (Review)
Review
The prevailing opioid crisis has necessitated the need to understand mechanisms leading to addiction and tolerance, the major contributors to overdose and death and to develop strategies for developing drugs for pain treatment that lack abuse liability and side-effects. Opioids are commonly used for treatment of pain and symptoms of inflammatory bowel disease. The significant effect of opioids in the gut, both acute and chronic, includes persistent constipation and paradoxically may also worsen pain symptoms. Recent work has suggested a significant role of the gastrointestinal microbiome in behavioral responses to opioids, including the development of tolerance to its pain-relieving effects. In this review, we present current concepts of gut-brain interaction in analgesic tolerance to opioids and suggest that peripheral mechanisms emanating from the gut can profoundly affect central control of opioid function.
Topics: Analgesics, Opioid; Animals; Brain; Drug Tolerance; Humans; Intestines
PubMed: 29145012
DOI: 10.1016/j.coph.2017.10.012 -
Annals of Palliative Medicine Mar 2020In this era of crisis and controversy surrounding opioid therapy, we must remember that cancer patients entrust us with supporting them through what might be the most... (Review)
Review
In this era of crisis and controversy surrounding opioid therapy, we must remember that cancer patients entrust us with supporting them through what might be the most difficult, and oftentimes final, period of their life. The factors that affect the benefits and risks of opioid use in cancer patients and the non-cancer population are quite different. In fact, opioid-associated deaths are 10 times less likely in the former than the latter population, suggesting that a reluctance to initiate opioids in cancer patients can risk under treatment of complex pain. In this review, we outline the considerations and evidence-based practices required to manage the clinical situations that challenge the judicious use of opioids in patients with cancer. A comprehensive review that enable us to better understand and quantify the root causes of variability in pain control, as well as risks of opioid misuse or abuse, would arm healthcare providers with the tools they need to implement multi-modal approaches to treatment planning.
Topics: Analgesics, Opioid; Cancer Pain; Disease Management; Humans; Opioid-Related Disorders; Pain Management; Pain Measurement
PubMed: 32233627
DOI: 10.21037/apm.2020.03.04