scholarly journals Biological Effects on μ-Receptors Affinity and Selectivity of Aryl Propenyl Chain Structural Modification on Diazatricyclodecane Derivatives

Molecules ◽  
2021 ◽  
Vol 26 (18) ◽  
pp. 5448
Author(s):  
Sandra Piras ◽  
Gabriele Murineddu ◽  
Giovanni Loriga ◽  
Antonio Carta ◽  
Enrica Battistello ◽  
...  

Opioid analgesics are clinically used to relieve severe pain in acute postoperative and cancer pain, and also in the long term in chronic pain. The analgesic action is mediated by μ-, δ-, and κ-receptors, but currently, with few exceptions for k-agonists, μ-agonists are the only ones used in therapy. Previously synthesized compounds with diazotricyclodecane cores (DTDs) have shown their effectiveness in binding opioid receptors. Fourteen novel diazatricyclodecanes belonging to the 9-propionyl-10-substituted-9,10-diazatricyclo[4.2.1.12,5]decane (compounds 20–23, 53, 57 and 59) and 2-propionyl-7-substituted-2,7-diazatricyclo[4.4.0.03,8]decane (compounds 24–27, 54, 58 and 60) series, respectively, have been synthesized and their ability to bind to the opioid μ-, δ- and κ-receptors was evaluated. Five of these derivatives, compounds 20, 21, 24, 26 and 53, showed μ-affinity in the nanomolar range with a negligible affinity towards δ- and κ-receptors and high μ-receptor selectivity. The synthesized compounds showed μ-receptor selectivity higher than those of previously reported methylarylcinnamyl analogs.

2002 ◽  
Vol 7 (4) ◽  
pp. 179-184 ◽  
Author(s):  
Dwight E Moulin ◽  
Alexander J Clark ◽  
Mark Speechley ◽  
Patricia K Morley-Forster

OBJECTIVE:To assess the prevalence, treatment and impact of chronic pain in Canada.METHODS:A stratified random sample of 2012 adult Canadians (weighted by sex, age and region according to 1996 census data) was surveyed by telephone in 2001 to determine the prevalence of chronic pain, defined as continuous or intermittent pain for at least six months. A second sample of 340 chronic pain sufferers who were taking prescription medication for their pain was studied in detail to determine current therapeutic approaches and to assess the social and economic impact of chronic pain.RESULTS:Chronic noncancer pain was reported by 29% of the respondents, with increased frequency in women and older age groups. The average duration of pain was 10.7 years and the average intensity was 6.3 (on a scale from 1 to 10), with 80% reporting moderate or severe pain. Anti-inflammatory agents were prescribed for 49% of respondents and opioid analgesics were prescribed for 22% (two-thirds of these were codeine). Almost 70% were worried about addiction potential, and one-third felt that strong analgesics should be reserved for terminal illnesses. Almost one-half were unable to attend social and family events, and the mean number of days absent from work in the past year due to chronic pain was 9.3.INTERPRETATION:Chronic noncancer pain is common in Canadian adults and has a major social and economic impact. Despite growing evidence supporting the efficacy and safety of major opioid analgesics for chronic noncancer pain, less than 10% of chronic pain patients taking prescription medication were treated with a major opioid. Chronic pain is undertreated in Canada, and major opioid analgesics are probably underutilized in the management of moderate to severe pain as part of a multidisciplinary treatment program.


Author(s):  
Ashim Gupta ◽  
Abdalla Bowirrat ◽  
Luis Llanos Gomez ◽  
David Baron ◽  
Igor Elman ◽  
...  

In the United States, amid the opioid overdose epidemic, nonaddicting/nonpharmacological proven strategies are available to treat pain and manage chronic pain effectively without opioids. Evidence supporting the long-term use of opioids for pain is lacking, as is the will to alter the drug-embracing culture in American chronic pain management. Some pain clinicians seem to prefer classical analgesic agents that promote unwanted tolerance to analgesics and subsequent biological induction of the “addictive brain”. Reward genes play a vital part in modulation of nociception and adaptations in the dopaminergic circuitry. They may affect various sensory and affective components of the chronic pain syndromes. The Genetic Addiction Risk Severity (GARS) test coupled with the H-Wave at entry in pain clinics could attenuate pain and help prevent addiction. The GARS test results identify high-risk for both drug and alcohol, and H-Wave can be initiated to treat pain instead of opioids. The utilization of H-Wave to aid in pain reduction and mitigation of hedonic addictive behaviors is recommended, notwithstanding required randomized control studies. This frontline approach would reduce the possibility of long-term neurobiological deficits and fatalities associated with potent opioid analgesics.


2021 ◽  
Author(s):  
Zachary S. Harmon ◽  
Emily N. Welch ◽  
Christina L. Ruby

The recent surge in opioid-related deaths has brought poor pain management practices to the forefront of our nation’s collective consciousness. However, improving treatments for chronic pain, substance use disorders (SUD), and comorbid expression of both requires a better understanding of the pathophysiology involved in their development. In this chapter, the authors present the argument that chronic pain and SUD can be conceptualized similarly from a biopsychosocial perspective to inform a better approach to treatment. The authors describe the common neurobehavioral mechanisms of SUD and chronic pain, then discuss the efficacy of several psychotherapeutic methods employed to combat chronic pain, addiction, and related disorders. Such methods may contribute to positive health outcomes in managing chronic pain and curbing drug addiction by reducing the role of opioid analgesics for long-term pain management.


2021 ◽  
Vol 10 (6) ◽  
Author(s):  
Janell Tully ◽  
Jai Won Jung ◽  
Anjana Patel ◽  
Alyson Tukan ◽  
Sameer Kandula ◽  
...  

Context: Chronic pain accounts for one of the most common reasons patients seek medical care. The financial burden of chronic pain on health care is seen by direct financial cost and resource utilization. Many risk factors may contribute to chronic pain, but there is no definite risk. Managing chronic pain is a balance between maximally alleviating symptoms by utilizing a therapeutic regimen that is safe for long-term use. Currently, non-opioid analgesics, NSAIDs, and opioids are some of the medical treatment options, but these have numerous adverse effects and may not be the best option for long-term use. However, Lidocaine can achieve both central and peripheral analgesic effects with relatively few side effects, which may be an ideal compound for managing chronic pain. Evidence Acquisition: This is a Narrative Review. Results: Infusion of lidocaine (2-(diethylamino)-N-(2,6-dimethylphenyl)acetamide), an amino-amide compound, is emerging as a promising option to fill the therapeutic void for treatment of chronic pain. Numerous studies have outlined dosing protocols for lidocaine infusion for the management of perioperative pain, outlined below. While there are slight variations in these different protocols, they all center around a similar dosing regimen to administer a bolus to reach a rapid steady state, followed by infusion for up to 72 hours to maintain the therapeutic analgesic effects. Conclusions: Lidocaine may be a promising pharmacologic solution with a low side effect profile that provides central and peripheral analgesia. Even though the multifaceted mechanism is not entirely understood yet, lidocaine may be a promising novel remedy in treating chronic pain in various conditions.


Author(s):  
Anton Yarikov ◽  
Maxim Shpagin ◽  
Iliya Nazmeev ◽  
Sergey Gorelov ◽  
Olga Perlmutter

The immediate and long-term results of treatment of 30 patients with severe pain syndrome of the lumbar region, who underwent operations on denervation of DOS, were studied. The aim of the study was to evaluate the effectiveness of minimally invasive technologies for the treatment of pain in the lumbar region (denervation of DOS), to study the near and distant results of these treatment methods. Denervation DOS is an effective minimally invasive method for the treatment of facet syndrome caused by spondylarthrosis. It allows in the early and distant postoperative periods to significantly reduce the pain syndrome and improve the quality of life of patients.


2020 ◽  
Vol 70 (suppl 1) ◽  
pp. bjgp20X711581
Author(s):  
Charlotte Greene ◽  
Alice Pearson

BackgroundOpioids are effective analgesics for acute and palliative pain, but there is no evidence base for long-term pain relief. They also carry considerable risks such as overdose and dependence. Despite this, they are increasingly prescribed for chronic pain. In the UK, opioid prescribing more than doubled between 1998 and 2018.AimAn audit at Bangholm GP Practice to understand the scale of high-strength opioid prescribing. The aim of the audit was to find out if indications, length of prescription, discussion, and documentation at initial consultation and review process were consistent with best-practice guidelines.MethodA search on Scottish Therapeutics Utility for patients prescribed an average daily dose of opioid equivalent ≥50 mg morphine between 1 July 2019 and 1 October 2019, excluding methadone, cancer pain, or palliative prescriptions. The Faculty of Pain Medicine’s best-practice guidelines were used.ResultsDemographics: 60 patients (37 females), average age 62, 28% registered with repeat opioid prescription, 38% comorbid depression. Length of prescription: average 6 years, 57% >5 years, 22% >10 years. Opioid: 52% tramadol, 23% on two opioids. Indications: back pain (42%), osteoarthritis (12%), fibromyalgia (10%). Initial consultation: 7% agreed outcomes, 35% follow-up documented. Review: 56% 4-week, 70% past year.ConclusionOpioid prescribing guidelines are not followed. The significant issues are: long-term prescriptions for chronic pain, especially back pain; new patients registering with repeat prescriptions; and no outcomes of treatment agreed, a crucial message is the goal is pain management rather than relief. Changes have been introduced at the practice: a patient information sheet, compulsory 1-month review for new patients on opioids, and in-surgery pain referrals.


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