Drug Research最新文献

{"title":"Therapeutic Potential of Sotagliflozin in Animal Models of Non-alcoholic Fatty Liver Disease with and without Diabetes.","authors":"Nitin J Deshmukh, M S Kalshetti, Mohan Patil, Manohar Nandanwar, Ganesh V Sangle","doi":"10.1055/a-2557-8927","DOIUrl":"10.1055/a-2557-8927","url":null,"abstract":"<p><p>Sotagliflozin, a dual SGLT1/2 inhibitor, enhances glucagon like peptide-1 (GLP-1) levels and GLP-1 receptor agonists are used to manage non-alcoholic fatty liver disease (NAFLD). Study investigates the effects of sotagliflozin on NAFLD, alone and combined with linagliptin, comparing outcomes in normoglycemic and hyperglycemic animal models.Obese fatty liver disease (FLD) model was induced by high-fat diet (HFD) feeding, while a diabetic non-alcoholic steatohepatitis (NASH) model was developed by administering a single dose of streptozotocin to neonatal mice, followed by HFD feeding post-weaning. At termination of the study, parameters including biochemical markers, inflammatory cytokines, hepatic lipid content, and histopathology were assessed.In NASH mice, sotagliflozin and linagliptin reduced hepatic triglycerides by 60% and 44%, respectively, and cholesterol by 46% and 49%. Their combination further decreased triglycerides by 68.5% and cholesterol by 83.9%. In FLD mice, sotagliflozin and linagliptin reduced triglycerides by 33% and 17%, respectively, and cholesterol by 46% and 21%. Combination treatment offered no benefit, reducing triglycerides by 38% and cholesterol by 27%. Both the treatments improved plasma fibroblast growth factor 21, hepatic interlukin-6, glucose tolerance, steatosis and mitigated fat pad weight, but their combination did not show additional benefit. However, combination treatment demonstrated added benefit in modulating NAFLD activity score, liver enzymes, glycogenated hepatic nuclei, plasma glucose and active GLP-1 levels.Study underscores sotagliflozin's potential to mitigate NAFLD and highlights the benefit of combining it with linagliptin in hyperglycemic NASH model, which showed limited efficacy in normoglycemic FLD mice.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"129-139"},"PeriodicalIF":1.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Levocabastine ameliorates cyclophosphamide-induced nephrotoxicity in Swiss albino mice via NF-κB/cleaved caspase-3/TGF-β signaling pathways.","authors":"Wasim Akram, Abul Kalam Najmi, M Mumtaz Alam, Syed Ehtaishamul Haque","doi":"10.1055/a-2552-2486","DOIUrl":"10.1055/a-2552-2486","url":null,"abstract":"<p><p>Cyclophosphamide (CP) is a potent anticancer drug, but nephrotoxicity is one of the vital organ toxicities that it causes as a side effect. We tried to evaluate the nephroprotective effect of levocabastine (LEV) in CP-induced nephrotoxicity in Swiss albino mice. Mice were given CP 200 mg/kg, i.p., once on the 7^th day. LEV (0.05 and 0.1 mg/kg, i.p.) and fenofibrate (FF) (80 mg/kg, p.o.) were given daily for 14 days. On the 15^th day, animals were sacrificed and kidneys were removed for examination. The docking study showed significant binding of LEV and FF against TGF-β1, which is a prime target molecule involved in nephrotoxicity. CP 200 group showed nephrotoxicity in terms of oxidative stress, apoptosis, inflammation, and fibrosis as manifested by decreased levels of SOD, catalase, GSH, blood urea nitrogen/creatinine (BUN/Cr) ratio, and increased TBARS, nitrite, TNF-α, IL-6, TGF-β1, IL-1β, urea, uric acid, creatinine, and BUN. A decrease in body weight (BW) and an increase in kidney weight (KW) with an increased KW/BW ratio was also observed. Cleaved caspase-3 and NF-κB expression was also increased. Histopathological aberrations, like renal corpuscle damage, Bowman's space widening, glomerulus, mesangium cell disintegration, atrophic podocytes, vacuolation, and fibrotic changes were also seen. LEV 0.1 and FF 80 significantly reversed these changes toward normal and showed nephroprotective potential. Thus, seeing the protective effect of LEV on CP-intoxicated mice, we conclude that LEV may be used as an adjuvant with CP in cancer, however, it needs more studies with the direct cancer model to confirm the claim.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"148-161"},"PeriodicalIF":1.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In situ Forming Nanoemulgel for Diabetic Retinopathy: Development, characterization, and in vitro efficacy assessment.","authors":"Soumya Singh, Poonam Kushwaha, Sujeet Gupta","doi":"10.1055/a-2517-4967","DOIUrl":"10.1055/a-2517-4967","url":null,"abstract":"<p><p>Diabetic retinopathy, the most common microvascular complication of diabetes mellitus, is the leading cause of vision impairment worldwide. Flavonoids with antioxidant properties have been shown to slow its progression. Myricetin, a flavonoid polyphenolic compound, possesses antioxidant properties, but its clinical use in ocular delivery is limited by poor aqueous solubility, stability, and bioavailability. Recently, in situ gels have gained interest as ocular drug delivery vehicles due to their ease of installation and sustained drug release. This study aimed to develop a myricetin-loaded thermoresponsive in situ nanoemulgel to enhance its efficacy in treating diabetic retinopathy. Nanoemulsions were developed via aqueous phase titration using Sefsol 218 as the oil phase, Kolliphore RH40 as the surfactant, and PEG 400 as the co-surfactant. Physicochemical evaluations identified formulation batch ISG17, consisting of 10% oil phase, 30% S_mix (1:2), and 60% distilled water, as the optimal formulation. The developed in situ nanoemulgel showed significant enhancement in corneal permeation and retention, which was further confirmed by fluorescence microscopy. Ocular tolerability was demonstrated through corneal hydration tests and histopathology investigations. The antioxidant potential of the myricetin-loaded nanoemulgel was assessed using the DPPH assay. Myricetin was found to be an efficient antioxidant, as indicated by its IC₅₀ values compared to ascorbic acid. The MTT cell viability assay results showed that the developed formulation effectively inhibits the proliferation of Y79 retinoblastoma cells, demonstrating comparable efficacy to the standard marketed preparation Avastin (Bevacizumab injection). In conclusion, the nanoemulsion formulation containing a thermoresponsive polymer for in situ gelling presents a promising drug delivery system, offering superior therapeutic efficacy and better patient compliance for the treatment of diabetic retinopathy.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"100-113"},"PeriodicalIF":1.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1α,25(OH)2D3 Regulates the TGF-β1/Samd Signaling Pathway Inhibition of Hepatic Stellate Cell Activation.","authors":"Yihan Zhao, Jianghao Fan, Jia Wang, Jie Wan, Haiyan Ma, Xiaoying Sha, Hongli Wang","doi":"10.1055/a-2463-5530","DOIUrl":"10.1055/a-2463-5530","url":null,"abstract":"<p><p>To investigate the effect of 1α,25(OH)₂D₃ on hepatic stellate cells and the mechanism of the TGF-β1/Smad signaling pathway.LX2 cells were treated with TGF-β1 and different concentrations of 1α,25(OH)₂D₃. Cell proliferation was assessed using the CCK8 assay to determine the optimal concentration of 1α,25(OH)₂D₃ activity. The cell cycle and apoptotic rates were evaluated using flow cytometry. The expressions of Samd2, Samd3, Samd4, and Samd7 was assessed by western blotting, whereas the expression of MMP1, MMP13, and TIMP-1 was detected by qPCR.Compared with the control group, the 1α,25(OH)₂D₃ group had a higher apoptotic rate of LX2 cells, the cell cycle was blocked from the G1 stage to the S stage, the expressions of Samd2, Samd7, MMP1, and MMP13 increased, while the expressions of Samd3, Samd4, and TIMP-1 decreased.1α,25(OH)₂D₃ inhibits hepatic stellate cell activation and exerts anti-hepatic fibrosis effects by downregulating the expression of Samd3, Samd4, TIMP-1 and upregulating the expression of Samd2, Samd4, MMP1, and MMP13.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"94-99"},"PeriodicalIF":1.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fragment-Based Drug Discovery of KIF11 Inhibitors for Glioblastoma Treatment: Molecular Insights and Therapeutic Potential.","authors":"Qais Ahmad Naseer, Cao Xuexian, Deng Yimai, Muhammad Ajmal Khan, Shengxia Chen","doi":"10.1055/a-2512-9183","DOIUrl":"10.1055/a-2512-9183","url":null,"abstract":"<p><p>Fragment based novel drug identification and its validation through use of molecular dynamics and simulations.Comparing primary microcephaly genes with glioblastoma expression profiles reveals potential oncogenes, with proteins that support growth and survival in neural stem/progenitor cells likely retaining critical roles in glioblastoma. Identifying such proteins in familial and congenital microcephalic disorders offers promising targets for brain tumor therapy. Among these, KIF11, a kinesin motor protein (KSP), stands out as a significant oncogene. Expression analyses across various cancer types, including glioblastoma, demonstrate its overexpression in brain tumor patients. Using a targeted fragment-based drug discovery approach, we explored alternative small molecule inhibitors for KIF11. Existing drugs, such as ispinesib, are limited by side effects and multidrug resistance. Through molecular docking and simulations, we identified three candidate drug fragments. Further analysis confirmed that Mol-121026 exhibits a more stable interaction with KIF11 compared to ispinesib. Detailed analyses indicate that Mol-121026 binds to the same active site as the reference drug, effectively inhibiting KIF11's mechano-chemical activity. Importantly, Mol-121026, a derivative of 3-phenyl-1H-pyrazol-5-carboxylic acid, offers a promising alternative due to its lower molecular complexity, ability to target allosteric sites, and potential for optimization into a potent and effective drug candidate. Our findings identified Mol-121026 as a top candidate with a docking score of -10.2 kcal/mol and MM/GBSA binding energy of -19.10 kcal/mol. Molecular dynamics simulations revealed stable interactions with key residues GLU116 and GLU118, supporting its potential as a promising KIF11 inhibitor.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"114-124"},"PeriodicalIF":1.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of Carbon Nanotubes in Breast Cancer Therapy.","authors":"Mahdis Tajabadi","doi":"10.1055/a-0945-1469","DOIUrl":"10.1055/a-0945-1469","url":null,"abstract":"<p><p>Conjugated single-walled carbon nanotubes (SWNT) have been shown to be promising in cancer-targeted accumulation and is biocompatible, easily excreted, and possesses little toxicity. The present study aims at reviewing the recent advancements in carbon nanotubes especially SWNT for improving the treatment of breast cancer. Nanotube drug delivery system is a potential high efficacy therapy with minimum side effects for future tumor therapy with low doses of drug.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"89-93"},"PeriodicalIF":1.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37100097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Review of Potentials of Carica Papaya Leaves in Dengue Viral Infection - Insights of Clinical and Preclinical Studies.","authors":"Naina Mohamed Pakkir Maideen, Rajkapoor Balasubramanian, Arun Shanmugam, Mirunalini Gobinath, Mohamed Harshath Jahir Hussain","doi":"10.1055/a-2509-8644","DOIUrl":"10.1055/a-2509-8644","url":null,"abstract":"<p><p>One of the most widespread arboviral diseases in the world, dengue virus disease (DVD) is primarily found in tropical and subtropical regions, affecting 129 countries. The main way that the dengue virus (DENV) spreads is through the bite of a female <i>Aedes aegypti</i> mosquito. Symptomatic therapy and supportive care are the primary methods of managing patients with DENV infection as there is currently no approved antiviral medication for this condition. Since the guidelines from the AYUSH Ministry, Government of India, recommend 10 ml of <i>carica papaya</i> leaf extract (CPLE) twice daily for seven days, to treat dengue fever clinically, we plan to review the potential of <i>carica papaya</i> in managing DENV infection.Using terms like dengue, dengue fever, dengue hemorrhagic fever, dengue shock syndrome, and <i>carica papaya</i>, the literature was searched in databases like Medline/PubMed Central/PubMed, Google Scholar, Science Direct, EBSCO, Scopus, Web of Science, EMBASE, Directory of open access journals (DOAJ), and reference lists to find articles relevant to the clinical, <i>in-vivo, in-vitro</i>, and <i>in-silico</i> studies evaluating the efficacy of <i>carica papaya</i> in the management of dengue viral infection. This review included English-language publications that supported the use of c<i>arica papaya</i> in the treatment of dengue fever, but it excluded publications that were duplicates.Numerous preclinical and clinical investigations, such as <i>in-vitro, in-vivo</i>, and <i>in-silico</i> studies, have identified <i>carica papaya's</i> anti-dengue potential. The pleiotropic effects of <i>carica papaya</i>, including its anti-thrombocytopenic activity, immunomodulatory effects, and larvicidal property against the <i>Aedes aegypti</i> mosquito species, have also been confirmed by numerous <i>in-vitro</i> and <i>in-vivo</i> studies. These effects can help patients with dengue fever by elevating their platelet count and alleviating other symptoms.To hasten recovery and reduce hospital stays, patients with DENV infection may take <i>carica papaya</i> leaf extract (CPLE) in addition to supportive care and symptomatic treatment. Additional randomized controlled clinical trials would be necessary to confirm the safety and effectiveness of CPLE in patients with DENV infection.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"49-59"},"PeriodicalIF":1.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WEE1 Inhibition by AZD1775 Augments Colorectal Cancer Cells Susceptibility to VE-822-induced DNA Damage and Apoptosis.","authors":"Ainaz Mihanfar, Faezeh Asghari, Maryam Majidinia","doi":"10.1055/a-2499-3067","DOIUrl":"10.1055/a-2499-3067","url":null,"abstract":"<p><p>WEE1 is a key tyrosine kinase involved in the cell cycle regulation with potent anticancer effects in various cancer types including colorectal cancer. Recent studies have focused on the potential of combinational inhibition of Ataxia Telangiectasia and Rad-3-related protein (ATR) and WEE1 in increasing apoptosis in cancer cells. Therefore, this study investigates the effects of inhibiting WEE1, by employing AZD1775, on colorectal cancer cells' susceptibility to VE-822-induced DNA damage and apoptosis.SW-480 and HT-29 cells were treated with AZD1775 and VE-822, alone and in combination. MTT assay was used to assess cell proliferation and viability. The mRNA levels of ATR, checkpoint kinase 1 (CHK1), WEE1, ribonucleotide reductase (RR) catalytic subunit M1 (RRM1) and RRM2 were measured by qRT-PCR. Cellular γ-(H2A histone family member X) H2AX levels were measured by Western blot. Analyses were conducted using ELISA to assess 8-Oxo-2'-deoxyguanosine (8-oxo-dG) levels. Lactate dehydrogenase (LDH) and ELISA death assays were used to assess apoptosis.The SW-480 and HT-29 cells have low proliferation rate when treated with VE-822 and AZD1775. The IC50 value for VE-822 was 1.3 μM and 1.6 μM in SW480 and HT-29, respectively. Also, this value for AZD1775 in SW480 was 140 nM and in HT-29 was 185 nM. The expression levels of ATR, CHK1, WEE1, RRM1, and RRM2 were significantly downregulated in both cell lines treated with combination of VE-822 and AZD1775 (P<0.05). DNA damage markers, including γ-H2AX and 8-oxo-dG were upregulated in these cells. Simultaneous treatment with VE-822 and AZD177 increased apoptosis capacity of both cell lines.The inhibition of WEE1 via AZD1775 potentiated the anticancer effects of ATR inhibitor, VE-822, in combating colorectal cancer via targeting DNA damage.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"66-75"},"PeriodicalIF":1.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thymoquinone Mediates Müller Cell Apoptosis via miR-29b/SP1 Pathway: A Potential Therapeutic Approach in Diabetic Retinopathy.","authors":"Khalid M Alkharfy, Ajaz Ahmad, Mohammad Raish, Maha F Alenazy","doi":"10.1055/a-2507-5528","DOIUrl":"10.1055/a-2507-5528","url":null,"abstract":"<p><p>This study aims to explore the therapeutic potential of thymoquinone (TQ) in DR by assessing its effects on Müller cell apoptosis through modulation of the miR-29b/SP1 pathway in a diabetic animal model.Healthy C57BL/6 mice (25 g) were used in the study. Retinal samples were collected from both normal and diabetic mice subjected to various treatments: TQ (1 mg/kg/day), glibenclamide (GLB, 250 mg/kg/day), sitagliptin (STG, 10 mg/kg/day), and metformin (MET, 5 mg/kg/day) over a period of 28 days. The study measured miR-29b and SP1 mRNA levels using qRT-PCR. Protein expressions of SP1, Bax, and bcl-2 were analyzed through western blotting, while Caspase-3 activity using an ELISA assay kit, and apoptosis levels by annexin V.TQ administration resulted in a 52% reduction in blood glucose levels. Similarly, GLB, STG, and MET treatments reduced blood glucose by 60%, 57%, and 61%, respectively (<i>p<0.05</i>). In addition, TQ upregulated miR-29b by 51.28% and downregulated SP1 mRNA by 32.52% (<i>p<0.05</i>). Bax protein expression levels were decreased by 64.99%, while Bcl-2 protein expression increased by 62.92% in the TQ treatment group as compared to the untreated diabetic controls. Furthermore, Caspase-3 activity was downregulated by 40.03% with TQ treatment (<i>p<0.05</i>). Interestingly, the effect TQ on SP1 mRNA expression was inhibited by a miR-29b blocker (<i>p<0.05</i>), while an miR-29b mimic enhanced this effect; this was associated with a mitigation of apoptosis of retinal Müller cells as measured by flow cytometry (<i>p<0.05</i>).These results indicate that TQ might be a possible option for DR <i>via</i> its effect on the miR-29b/SP1 pathway; and therefore, playing a significant role in the mechanism against cell death.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"76-83"},"PeriodicalIF":1.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repeated injections of isovaline lead to analgesic tolerance and cross-tolerance to salicylate but not to morphine in male mice.","authors":"Maryam Moghimian, Reza Nazari-Motlagh, Seyed Sajjad Alavi-Kakhki, Mahdi Khorsand Ghaffari, Elham Akbari, Masoumeh Fani, Mehdi Sadegh, Masoumeh Gholami","doi":"10.1055/a-2481-6129","DOIUrl":"10.1055/a-2481-6129","url":null,"abstract":"<p><p>Tolerance to the antinociceptive effects of opioids is a major concern. Studies have shown that chronic use of non-steroidal anti-inflammatory (NSAIDs) causes significant tolerance and cross-tolerance to morphine. Chronic NSAIDs use can increase the risk of certain diseases, such as peptic ulcers, and exacerbate others, like heart failure. Therefore, developing novel pharmacological approaches could provide considerable benefits for chronic therapeutic procedures. Isovaline with a chemical structure similar to glycine and GABA induce a significant analgesic effect through GABA-B receptors. In this study, we investigated the impact of both short-term and long-term use of isovaline on the immediate response to pain, as well as the development of analgesic tolerance through daily injection (i.p.) of isovaline (100 mg/kg) for 5 days in male Balb/c mice. Additionally, on day 6, we examined the potential for cross-tolerance between isovaline and sodium salicylate (300 mg/kg) or morphine (5 mg/kg). The findings showed that isovaline injection resulted in a delayed onset of analgesic effect, a lowered peak effect, and less cumulative pain relief compared with sodium salicylate and morphine. This analgesic effect gradually decreased over the five days of isovaline injection. When sodium salicylate was injected into isovaline-tolerant mice, the antinociceptive effect decreased, suggesting cross-tolerance to sodium salicylate. However, no such tolerance was observed following morphine injection. Accordingly, it seems that chronic isovaline may interact with the sodium salicylate analgesic pathway but not with morphine.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"60-65"},"PeriodicalIF":1.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}