Antonios M Diab, Hailey Stack, Brendan T McKeown, Bruce C Carleton, Kerry B Goralski
{"title":"Systematic Review of Health Canada Authorized Clinical Therapeutic Trials for the Treatment or Prevention of Coronavirus Disease 2019 (COVID-19).","authors":"Antonios M Diab, Hailey Stack, Brendan T McKeown, Bruce C Carleton, Kerry B Goralski","doi":"10.1139/cjpp-2024-0055","DOIUrl":"https://doi.org/10.1139/cjpp-2024-0055","url":null,"abstract":"<p><p>In response to the COVID-19 pandemic, Canadian clinical researchers pivoted their research programs to investigate repurposing drugs, accelerating the development of experimental therapies, and developing novel disease-specific treatments. This systematic review analyzes the trial design, participant characteristics, and reported outcomes of all Health Canada authorized clinical trials of therapeutics to prevent or treat COVID-19 with published results as of March 2023. We conclude that there is a need for adaptive clinical trial designs, broader pan-Canadian clinical trial networks, more targeted participant recruitment to facilitate increased diversity and inclusion, and standardization in reporting participant characteristics, outcome measurement, and follow-up. Finally, guided by our findings, we make recommendations for improved clinical trial designs when faced with an emerging disease.</p>","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrea Sk Pop, Maria D Danila, Silvia Giuchici, Darius G Buriman, Bogdan M Lolescu, Adrian Sturza, Danina M Muntean, Ana Lascu
{"title":"Epicardial Adipose Tissue As Target of the Incretin-Based Therapies in Cardio-Metabolic Pathologies: A Narrative Review.","authors":"Andrea Sk Pop, Maria D Danila, Silvia Giuchici, Darius G Buriman, Bogdan M Lolescu, Adrian Sturza, Danina M Muntean, Ana Lascu","doi":"10.1139/cjpp-2024-0384","DOIUrl":"https://doi.org/10.1139/cjpp-2024-0384","url":null,"abstract":"<p><p>The epicardial adipose tissue (EAT) serves in physiological conditions as a mechanical and thermal myocardial protective layer, as well as a readily available lipid-storage unit. In pathological conditions, EAT expansion becomes deleterious and is currently recognized as an independent risk factor for the progression of cardiovascular diseases. The EAT phenotypic shift from protective to pro-inflammatory/pro-oxidant is facilitated by the presence of metabolic diseases (obesity, metabolic syndrome, and diabetes), which further increase its expansion and dysregulation, favor the occurrence of complications (mainly atrial fibrillation), and promote progression towards heart failure. Glucagon-like peptide-1 (GLP-1) receptor agonists are novel antidiabetic medications belonging to the incretin class that have demonstrated efficacy beyond glycemic control, in terms of weight reduction and cardio-renal protection in patients with type 2 diabetes mellitus. The GLP-1 receptors and glucose-dependent insulinotropic polypeptide (GIP) receptors are expressed in the human EAT and are targeted by an increasing number of pharmacological agonists, with pleiotropic protective effects on EAT structure and function. Herein we review the literature characterizing the benefits of GLP-1 and GIP receptors activation by single and dual agonists with particular emphasis on their effects on EAT and highlight the role of incretin-based therapy for the management of cardio-metabolic pathologies.</p>","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sydney M Polson, Joshua P Thornburg, Benjamin D McNair, Christian Z Cook, Elizabeth A Straight, Kevin C Fontana, Caleb R Hoopes, Sreejayan Nair, Danielle R Bruns
{"title":"Right ventricular dysfunction in preclinical models of type I and type II diabetes.","authors":"Sydney M Polson, Joshua P Thornburg, Benjamin D McNair, Christian Z Cook, Elizabeth A Straight, Kevin C Fontana, Caleb R Hoopes, Sreejayan Nair, Danielle R Bruns","doi":"10.1139/cjpp-2024-0195","DOIUrl":"10.1139/cjpp-2024-0195","url":null,"abstract":"<p><p>Diabetic cardiomyopathy (DCM) is a growing clinical entity and major health burden characterized by comorbid diabetes mellitus and heart failure. DCM has been commonly associated with impaired function of the left ventricle (LV); however, DCM likely also occurs in the right ventricle (RV) which has distinct physiology and pathophysiology from the LV. RV dysfunction is the strongest determinant of mortality in several clinical contexts yet remains poorly studied in diabetes. We investigated RV-specific pathophysiology using two models of diabetes-a well-characterized type 2 diabetes (T2DM) model of high-fat diet and low-dose streptozotocin (STZ) in the mouse and a large animal model of type I diabetes in domestic pigs rendered diabetic with STZ. RV global and systolic function deteriorated with diabetes, alongside hypertrophic and fibrotic remodeling. We report evidence of impaired RV insulin sensitivity, dysregulated RV metabolic gene expression, and impaired mitochondrial dynamics. Importantly, while some of these outcomes were similar to those widely reported in the LV, others were not, such as unchanged antioxidant gene expression and regulators of fatty acid uptake. Importantly, these RV-specific changes occurred in both male and female T2DM mice, together emphasizing the importance of distinguishing the RV from the LV when studying DCM and begging the consideration of RV-specific therapies.</p>","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"86-97"},"PeriodicalIF":1.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kirishani Kesavan, Sheethal Panchakshari, Haya Abdelwahab, Elena Stephanie Gomez Rabelo, Ketul R Chaudhary
{"title":"Endothelial characteristics of cardiac stem cell antigen-1 expressing cells and their relevance to right ventricular adaptation.","authors":"Kirishani Kesavan, Sheethal Panchakshari, Haya Abdelwahab, Elena Stephanie Gomez Rabelo, Ketul R Chaudhary","doi":"10.1139/cjpp-2024-0244","DOIUrl":"10.1139/cjpp-2024-0244","url":null,"abstract":"<p><p>A growing body of evidence suggest that the stem cell antigen-1 expressing (Sca-1<sup>+</sup>) cells in the heart may be the cardiac endothelial stem/progenitor cells. Their endothelial cell (EC) functions, and their role in right ventricle (RV) physiology and pathophysiology of right heart failure (RHF) remains poorly defined. This study investigated EC characteristics of rat cardiac Sca-1<sup>+</sup> cells, assessed spatial distribution and studied changes in Sca-1<sup>+</sup> cells during RV remodelling in monocrotaline (MCT) model of pulmonary hypertension and RV remodeling. First, flow-cytometry analysis of adult male and female Sprague Dawley (SD) and Fischer CDF rat heart cells was performed, and we observed that the majority of Sca-1<sup>+</sup> cells also expressed CD31, an EC marker. Furthermore, Sca-1<sup>+</sup> cells showed acetylated low-density lipoprotein (ac-LDL) uptake and lectin binding similar to CD31<sup>+</sup> cells from the same heart. The Sca-1<sup>+</sup> cells also demonstrated network formation when plated on Matrigel. In the MCT treated rats, we observed increase in RV hypertrophy that correlated with the reduction in the abundance of Sca-1<sup>+</sup>CD31<sup>+</sup> cells in the RV. Together, the cardiac Sca-1<sup>+</sup> cells in the heart are endothelial stem/progenitor-like cells. These cells have higher abundance in the RV and may play a role in RV adaptation.</p>","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"98-110"},"PeriodicalIF":1.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ali A Husain, Ravikumar Manickam, Jonah Gordon, Sandhya Santhana, Katarzyna Mizgalska, Wayne C Guida, Srinivas M Tipparaju, Kirpal S Bisht
{"title":"Chemical synthesis, in vitro testing, and in silico Nampt-based molecular docking of novel aniline aromatic ring-substituted 2-aminothiazole analogs.","authors":"Ali A Husain, Ravikumar Manickam, Jonah Gordon, Sandhya Santhana, Katarzyna Mizgalska, Wayne C Guida, Srinivas M Tipparaju, Kirpal S Bisht","doi":"10.1139/cjpp-2024-0211","DOIUrl":"10.1139/cjpp-2024-0211","url":null,"abstract":"<p><p>The heterocyclic 2-aminothiazoles scaffolds are used in a wide range of therapeutic applications against various diseases for its antioxidant, anti-inflammatory, antimicrobial and anticancer actions. In this study, we synthesized novel aniline aromatic ring-substituted 2-aminothiazole derivatives. Molecular docking was performed using Glide module of the Schrödinger Suite to fit compounds JG-49, JG-62, and KBA-18 against the Nicotinamide phosphoribosyl transferase (Nampt) enzyme, an intracellular regulator of nicotinamide adenine dinucleotide (NAD) redox cofactor involved in energy metabolism and epigenetics and are implicated in aging and metabolic diseases. The three compounds viz. JG-49, JG-62, and KBA-18 showed an increase in Nampt enzymatic activity in vitro. All three substituted derivatives of 2-aminothiazole showed no cytotoxicity with the mouse C2C12 myoblasts cultures assessed with the MTT cell viability assay. Moreover, the wound closure of the mouse C2C12 myoblasts in vitro displayed no significant difference between the treatment groups of the 2-aminothiazole derivatives compared with the control naïve and DMSO treated myoblasts cultures, except for the 2-aminothiazole substituted derivatives JG-62 and KBA-18, which showed a significant increase in the wound closure compared with the control cells at different concentrations. Taken together, we demonstrated that 2-aminothiazole substituted derivatives provide enhanced Nampt activity, wound closure, and no cytotoxic effects in vitro. Further studies will allow to improve the substitution of 2-aminothiazole derivatives and test their potential therapeutic applications.</p>","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"75-85"},"PeriodicalIF":1.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Meghan Victoria McCue, Irena A Rebalka, Tom Hawke, David A MacLean
{"title":"Examining tissue-level changes in Doxorubicin accumulation and Nitric Oxide formation in skeletal muscle and tumours in a mouse model of breast cancer.","authors":"Meghan Victoria McCue, Irena A Rebalka, Tom Hawke, David A MacLean","doi":"10.1139/cjpp-2024-0368","DOIUrl":"https://doi.org/10.1139/cjpp-2024-0368","url":null,"abstract":"<p><strong>Introduction: </strong>Doxorubicin is a commonly used chemotherapy that rapidly accumulates in skeletal muscle and disrupts nitric oxide (NO) formation. However, studies investigating these effects have largely been performed in tumour-free models, therefore it remains unknown whether intramuscular accumulation and disruptions to nitric oxide content persist during tumour growth.</p><p><strong>Methodology: </strong>Female C57bl/6 mice (n = 8/group) were randomly assigned to true control, Doxorubicin control, tumour only, or tumour plus Doxorubicin groups. Tumours were grown for 21, 24, or 28 days using E0771 cells. Doxorubicin was administered as a single 10 mg/kg intraperitoneal dose on day 21.</p><p><strong>Results: </strong>Doxorubicin accumulation was similar in muscle with and without tumours present. Doxorubicinol, a metabolite of Doxorubicin, was elevated (p<0.05) in 24-day tumour+Doxorubicin compared to Doxorubicin alone. NO was similar across all groups in muscle; however, tumour NO was 15-fold higher at day 21 compared to 24, or 28 days (p<0.05).</p><p><strong>Conclusion: </strong>The results confirm that Doxorubicin is sequestered in skeletal muscle when a tumour is present, which may impact bioavailability. Tumour growth transiently increased intramuscular Doxorubicinol, potentially exacerbating the toxicity of the drug. Earlier stage tumour growth appeared to profoundly elevate NO, which could suggest temporal angiogenesis and vasodilation to facilitate growth.</p>","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Causality Assessment of Adverse Events by Healthcare Professionals in an Academic Hospital Setting: A Descriptive Retrospective Study.","authors":"Sonia Corbin, Maude Lavallée, Pallavi Pradhan, Magalie Thibault, Julie Méthot, Laura Blonde Guefack Djiokeng, Anick Berard, Marie-Eve Piché, Fernanda Raphael Escobar Gimenes, Rosalie Darveau, Isabelle Cloutier, Jacinthe Leclerc","doi":"10.1139/cjpp-2024-0268","DOIUrl":"https://doi.org/10.1139/cjpp-2024-0268","url":null,"abstract":"<p><strong>Background: </strong>Assessing the causality of a drug product-related adverse event (AE) is a very important aspect of pharmacovigilance. However, it is unclear whether AEs are investigated for causality in a hospital setting.</p><p><strong>Objectives: </strong>The aims of this study were to: 1) evaluate the proportion of AEs for which causality is sought and, 2) list the causality assessment (CA) tools used by healthcare professionals.</p><p><strong>Methods: </strong>This retrospective study includes 500 randomized patients (125 patients/year) admitted to a tertiary care academic hospital between 2018-2021. Electronic medical records were reviewed and relevant variables were extracted: 1) demographic, 2) hospitalization, 3) drug product, 4) AE and, 5) CA. A descriptive analysis was carried out (median, minimum-maximum, proportion) to characterize our sample.</p><p><strong>Results: </strong>The characteristic of our sample was as follows: median age 69 years old (range: 21-96 yrs), 43.6% female, median comorbidities/patient 4 (0-12), and median hospital stay of 3 days (1-19). We identified a total of 9,568 drug products and 2,541 AEs, among these, 302 (8.4%) were SAEs. No CA (n=0) or CA tools (n=0) were found in our sample.</p><p><strong>Conclusion: </strong>In this study, we report that no AEs, whether serious or non-serious, were subject to documented CA.</p>","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Histamine H<sub>3</sub> receptor activation increases the firing of striatal medium spiny neurons in slices from infantile rats.","authors":"Carolina González-Sandoval, Isabel Godínez-Ramos, José-Antonio Arias-Montaño, Jaime Barral","doi":"10.1139/cjpp-2024-0240","DOIUrl":"https://doi.org/10.1139/cjpp-2024-0240","url":null,"abstract":"<p><p>Striatal medium spiny neurons (MSN) form two subpopulations (MSN-D1<sub></sub> and MSN-D2<sub></sub>) according to the expression of dopamine D1<sub></sub> or D2<sub></sub> receptors and their target regions. The activation of postsynaptic histamine H1<sub></sub> and H2<sub></sub> receptors increases MSN-D1<sub></sub> and MSN-D2<sub></sub> excitability. Since MSN also express H3<sub></sub> receptors (H3<sub></sub>Rs), in this work we explored the effect of their activation on MSN firing. Electrophysiological recordings (whole-cell patch-clamp, current-clamp mode) were conducted on forebrain slices from infantile rats (12-16 postnatal days). In both MSN-D1<sub></sub> and MSN-D2<sub></sub> perfusion with the H3<sub></sub>R agonist immepip (1 μM) increased neuronal firing evoked by current injection, an effect reproduced by R-α-methylhistamine (1 μM) and prevented by the antagonist clobenpropit (10 μM). Blockade of N- or P/Q-type voltage-activated calcium channels by ω-conotoxin-GVIA (1 μM) or ω-agatoxin-TK (400 nM) increased MSN firing but did not preclude the immepip effect. The potassium channel blockers 4-aminopyridine (1 mM) and tetraethylammonium (300 μM) increased neuronal firing and prevented the immepip action. Likewise, the KV<sub></sub>7 channel blocker XE-991 (10 μM) and the muscarinic receptor agonist carbachol (10 μM) increased MSN firing frequency and occluded the immepip effect. These data indicate that the activation of postsynaptic H3<sub></sub>Rs facilitates MSN-D1<sub></sub> and MSN-D2<sub></sub> firing by inhibiting KV<sub></sub>7 potassium channels.</p>","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Antonio Viana do Nascimento Filho, Filipe Fernandes Stoyell-Conti, Akolkar Gauri, Lara Susan Silva Lima, Nathalia Bernardes, Maria Claudia Irigoyen, Pawan Singal, Kátia De Angelis, Danielle da Silva Dias
{"title":"Vitamin C protects against doxorubicin induced skeletal muscle atrophy: Role of oxidative stress.","authors":"Antonio Viana do Nascimento Filho, Filipe Fernandes Stoyell-Conti, Akolkar Gauri, Lara Susan Silva Lima, Nathalia Bernardes, Maria Claudia Irigoyen, Pawan Singal, Kátia De Angelis, Danielle da Silva Dias","doi":"10.1139/cjpp-2024-0154","DOIUrl":"https://doi.org/10.1139/cjpp-2024-0154","url":null,"abstract":"<p><p>Doxorubicin is known for its significant cardiotoxicity, driven in part by elevated oxidative stress (OS). Furthermore, preclinical models have demonstrated that doxorubicin induces skeletal muscle atrophy. While vitamin C has been recognized as a valuable pharmacological intervention for mitigating cardiac toxicity, its impact on doxorubicin-induced skeletal muscle atrophy is still to be determined. Therefore, this study aimed to investigate the effects of vitamin C on the skeletal muscle of rats subjected to doxorubicin exposure. Indeed, doxorubicin led to a reduction in body weight and gastrocnemius muscle weight. It also increased H2O2, protein oxidation and lipid peroxidation in the gastrocnemius. On the other hand, vitamin C was able to prevent the loss in skeletal muscle mass, as well as, the increase in markers of oxidative stress. In addition, negative correlations between gastrocnemius muscle mass and markers of cell damage were found. In conclusion, vitamin C emerges as a protective agent against doxorubicin-induced skeletal muscle atrophy and oxidative stress. This suggests its potential application as a prophylactic measure for patients undergoing doxorubicin treatment. Keywords: Doxorubicin, Vitamin C, Oxidative Stress, Skeletal Muscle.</p>","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
James M Duerksen, Matthew Ramjiawan, Julia Witt, Shirley Fitzpatrick-Wong, Paramjit S Tappia, Bram Ramjiawan, Behzad Mansouri, Jitender Sareen, Erin Knight
{"title":"The addictive process of opioids: current and novel interventions in opioid use disorder.","authors":"James M Duerksen, Matthew Ramjiawan, Julia Witt, Shirley Fitzpatrick-Wong, Paramjit S Tappia, Bram Ramjiawan, Behzad Mansouri, Jitender Sareen, Erin Knight","doi":"10.1139/cjpp-2024-0281","DOIUrl":"10.1139/cjpp-2024-0281","url":null,"abstract":"<p><p>The growing epidemic of opioid misuse presents numerous challenges for healthcare practitioners and patients alike as friction exists between ease of use and efficacy, and potential for overuse and addiction. With over 82 000 deaths related to opioid overdose in North America in 2020, it is imperative to gain a better understanding of the underlying mechanisms behind the addiction process, as well as the current methods being used in the arsenal against this disease. The current best pharmacological approaches for mediating opioid use disorder are methadone, buprenorphine, naltrexone, and naloxone, which act on opioid receptors to produce diverse effects based upon the patients' needs. The variety of effects that these drugs produce, which include removing opioid withdrawal, reversing overdose effects, and blocking opioid properties, makes this arsenal of therapeutics a global necessity in addressing the opioid use epidemic. Accordingly, this narrative review provides a summary of the available data regarding the physiological processes by which opioid addiction takes place and discusses the current and future potential of interventional methods used to mitigate opioid use disorder. The mechanisms of action and subsequent functional outcomes must be understood to reduce the number of opioid-related deaths worldwide.</p>","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}