Pharmacological Reports最新文献

{"title":"Comprehensive evaluation of ibuprofenate amino acid isopropyl esters: insights into antioxidant activity, cytocompatibility, and cyclooxygenase inhibitory potential.","authors":"Magdalena Perużyńska, Anna Nowak, Anna Muzykiewicz-Szymańska, Łukasz Kucharski, Joanna Klebeko, Karolina Bilska, Ewelina Kopciuch, Radosław Birger, Marek Droździk, Paula Ossowicz-Rupniewska","doi":"10.1007/s43440-024-00666-6","DOIUrl":"10.1007/s43440-024-00666-6","url":null,"abstract":"<p><p>Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for pain relief and inflammation management, but there are challenges related to poor solubility and bioavailability. We explored modifications of ibuprofen (IBU) by forming ionic pairs using amino acid alkyl esters to enhance solubility without compromising the ability to inhibit cyclooxygenase (COX)-1 and COX-2). We comprehensively evaluated the pharmacological properties of the IBU derivatives, focusing on antioxidant activity (based on the ability to scavenge DPPH and ABTS), biocompatibility (using human dermal fibroblasts), and COX inhibitory potential. The antioxidant activity assays significantly enhanced DPPH scavenging activity for several IBU derivatives, particularly [L-SerOiPr][IBU], suggesting potential therapeutic benefits. There was enhanced cell viability with select derivatives, indicating possible stimulatory effects on cellular proliferation. Finally, predominant COX-1 inhibition across derivatives was consistent with IBU's profile. This study provides insights into the pharmacological properties of IBU amino acid derivatives, highlighting their potential as therapeutic agents. Further exploration into structure-activity relationships and in vivo efficacy warranted to advance these derivatives toward clinical applications, offering prospects for novel NSAIDs with enhanced efficacy and reduced side effects.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"1470-1481"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11582120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthetic free fatty acid receptor (FFAR) 2 agonist 4-CMTB and FFAR4 agonist GSK13764 inhibit colon cancer cell growth and migration and regulate FFARs expression in in vitro and in vivo models of colorectal cancer.","authors":"Agata Binienda, Katarzyna Owczarek, Maciej Sałaga, Jakub Fichna","doi":"10.1007/s43440-024-00667-5","DOIUrl":"10.1007/s43440-024-00667-5","url":null,"abstract":"<p><strong>Introduction: </strong>Free fatty acid receptors (FFARs) are G protein-coupled receptors that divide into 4 subtypes; FFAR2 and FFAR3 are activated by short-chain fatty acids, while FFAR1 and FFAR4 - by long-chain fatty acids. Recent studies show the potential involvement of FFARs in the pathophysiology of colorectal cancer (CRC). A decrease in FFAR2 and FFAR4 gene expression is observed in patients with CRC. The aim of our study was to evaluate the anti-cancer effect of FFAR2 and FFAR4 stimulation by selective synthetic agonists in in vitro and in vivo models of CRC.</p><p><strong>Materials and methods: </strong>FFAR2 agonist, 4-CMTB, and FFAR4 agonist, GSK137647 were used. Cell viability (CCD 841 CoN and SW-480) was determined after 48 h incubation with tested compounds using MTT assay. Real-time qPCR and Western Blot were used to identify changes in FFARs expression. Migration and invasion were characterized by commercially available tests. Colitis-associated CRC (CACRC) mouse model was induced by azoxymethane and dextran sodium sulfate.</p><p><strong>Results: </strong>4-CMTB and GSK137647 significantly reduced cancer cell growth as well as migration and invasion capacities. Both synthetic compounds increased FFAR2 and FFAR4 expression in SW-480 cells. Neither 4-CMTB nor GSK137647 influenced the course of AOM/DSS-induced CACRC in mice, however, 4-CMTB elevated FFAR2 protein expression in mouse tissues.</p><p><strong>Conclusion: </strong>We presented that stimulation of FFAR2 and FFAR4 may inhibit CRC cell viability and migration and that the FFAR2 and FFAR4 expression decreased in CRC can be restored by treatment with respective agonists, indicating new promising pharmacological targets in CRC treatment.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"1403-1414"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11582145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of 5-HT₇ receptors in the mouse dentate gyrus does not affect theta-burst-induced plasticity at the perforant path synapse.","authors":"Marcin Siwiec, Bartosz Bobula, Michal Kielbinski, Nikola Multan, Grzegorz Hess, Krzysztof Tokarski","doi":"10.1007/s43440-024-00674-6","DOIUrl":"10.1007/s43440-024-00674-6","url":null,"abstract":"<p><strong>Background: </strong>The study examined the effects of 5-HT₇ receptor activation on GABAergic transmission within the dentate gyrus and plasticity at the glutamatergic perforant path input.</p><p><strong>Methods: </strong>Immunofluorescence imaging was performed using transverse hippocampal slices from transgenic mice expressing green fluorescent protein (GFP) under the Htr7 promoter. This was followed by whole-cell patch clamp electrophysiological recordings assessing the effects of pharmacologically activating 5-HT₇ receptors on spontaneous inhibitory postsynaptic currents recorded from dentate granule cells and hilar mossy cells-two glutamatergic neuron types present in the dentate gyrus. Extracellular recordings of field excitatory postsynaptic potentials were then performed to assess whether 5-HT₇ receptor activation influenced theta-burst stimulation-evoked plasticity of the perforant path synaptic input.</p><p><strong>Results: </strong>It was found that parvalbumin and somatostatin interneurons in the dentate gyrus expressed GFP, which suggests they express 5-HT₇ receptors. However, activation of 5-HT₇ receptors had no effect on GABAergic transmission targeting mossy cells or granule cells. There was also no effect of 5-HT₇ receptor activation on perforant path plasticity either with intact or blocked GABA_A receptor signaling.</p><p><strong>Conclusion: </strong>The presence of 5-HT₇ receptors in a subset of parvalbumin and somatostatin interneurons in the mouse dentate gyrus could mean that they are involved in the inhibitory control of dentate gyrus activity. However, this potential effect was not evident in slice recordings of inhibitory transmission targeting principal cells and did not affect perforant path plasticity. Further experiments are needed to fully elucidate the functional role of these receptors in the dentate gyrus.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"1377-1389"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11582198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drugs with glutamate-based mechanisms of action in psychiatry.","authors":"Adrian Andrzej Chrobak, Marcin Siwek","doi":"10.1007/s43440-024-00656-8","DOIUrl":"10.1007/s43440-024-00656-8","url":null,"abstract":"<p><p>Psychopharmacotherapy of major psychiatric disorders is mostly based on drugs that modulate serotonergic, dopaminergic, or noradrenergic neurotransmission, either by inhibiting their reuptake or by acting as agonists or antagonists on specific monoamine receptors. The effectiveness of this approach is limited by a significant delay in the therapeutic mechanism and self-perpetuating growth of treatment resistance with a consecutive number of ineffective trials. A growing number of studies suggest that drugs targeting glutamate receptors offer an opportunity for rapid therapeutic effect that may overcome the limitations of monoaminergic drugs. In this article, we present a review of glutamate-modulating drugs, their mechanism of action, as well as preclinical and clinical studies of their efficacy in treating mental disorders. Observations of the rapid, robust, and long-lasting effects of ketamine and ketamine encourages further research on drugs targeting glutamatergic transmission. A growing number of studies support the use of memantine and minocycline in major depressive disorder and schizophrenia. Amantadine, zinc, and Crocus sativus extracts yield the potential to ameliorate depressive symptoms in patients with affective disorders. Drugs with mechanisms of action based on glutamate constitute a promising pharmacological group in the treatment of mental disorders that do not respond to standard methods of therapy. However, further research is needed on their efficacy, safety, dosage, interactions, and side effects, to determine their optimal clinical use.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"1256-1271"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11582293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Personalization of pharmacotherapy with sirolimus based on volumetric absorptive microsampling (VAMS) in pediatric renal transplant recipients-from LC-MS/MS method validation to clinical application.","authors":"Arkadiusz Kocur, Agnieszka Czajkowska, Kamila Rębis, Jacek Rubik, Mateusz Moczulski, Bartłomiej Kot, Maciej Sierakowski, Tomasz Pawiński","doi":"10.1007/s43440-024-00663-9","DOIUrl":"10.1007/s43440-024-00663-9","url":null,"abstract":"<p><strong>Background: </strong>The benefits of pharmacotherapy with sirolimus (SIR) in pediatric transplant recipients are well established. Traditionally, whole blood samples have been used to measure SIR concentrations. Volumetric Absorptive Microsampling (VAMS) is an alternative sampling strategy suitable for Therapeutic Drug Monitoring (TDM). In this study, we developed and validated two liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods for determining SIR concentrations in whole blood (WB) and capillary whole blood samples collected using a VAMS-Mitra™ device.</p><p><strong>Methods: </strong>We used protein precipitation during WB sample preparation and dispersive liquid-liquid microextraction (DLLME) with methyl tert-butyl ether for VAMS sample preparation to optimise the analyte extraction process. The described validation protocols were cross-validated, confirming the equivalence of the whole-blood and VAMS-based methods. Furthermore, the developed methods were evaluated in two three-level rounds of an external proficiency-testing scheme.</p><p><strong>Results: </strong>The analytical methods were successfully validated within the calibration range of SIR (0.5-60 ng/ml). The validation parameters met the European Medicines Agency (EMA) and the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDM&CT) acceptance criteria. No hematocrit (tested in the range of 24.3-64.1%), matrix, or carry-over effects were observed. Cross-validation confirmed the interchangeability between VAMS-LC-MS/MS and WB-LC-MS/MS methods. The developed methods were successfully implemented for SIR determination in 140 clinical samples (70 each of WB and VAMS) from pediatric renal transplant recipients, demonstrating their practicality and reliability.</p><p><strong>Conclusion: </strong>The VAMS-based method has been rigorously tested and is clinically equivalent to the reference WB-LC-MS/MS method. Additionally, clinical validation confirmed the utility of the presented methods for TDM of the SIR in the pediatric population after renal transplantation.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"1443-1455"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11582253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psilocybin and the glutamatergic pathway: implications for the treatment of neuropsychiatric diseases.","authors":"Izabela Szpręgiel, Agnieszka Bysiek","doi":"10.1007/s43440-024-00660-y","DOIUrl":"10.1007/s43440-024-00660-y","url":null,"abstract":"<p><p>In recent decades, psilocybin has gained attention as a potential drug for several mental disorders. Clinical and preclinical studies have provided evidence that psilocybin can be used as a fast-acting antidepressant. However, the exact mechanisms of action of psilocybin have not been clearly defined. Data show that psilocybin as an agonist of 5-HT2A receptors located in cortical pyramidal cells exerted a significant effect on glutamate (GLU) extracellular levels in both the frontal cortex and hippocampus. Increased GLU release from pyramidal cells in the prefrontal cortex results in increased activity of γ-aminobutyric acid (GABA)ergic interneurons and, consequently, increased release of the GABA neurotransmitter. It seems that this mechanism appears to promote the antidepressant effects of psilocybin. By interacting with the glutamatergic pathway, psilocybin seems to participate also in the process of neuroplasticity. Therefore, the aim of this mini-review is to discuss the available literature data indicating the impact of psilocybin on glutamatergic neurotransmission and its therapeutic effects in the treatment of depression and other diseases of the nervous system.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"1297-1304"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11582295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of levetiracetam and ethanol on memory, selected neurotransmitter levels, oxidative stress parameters, and essential elements in rats.","authors":"Ewa Zwierzyńska, Michał Klimczak, Marzenna Nasiadek, Joanna Stragierowicz, Bogusława Pietrzak","doi":"10.1007/s43440-024-00659-5","DOIUrl":"10.1007/s43440-024-00659-5","url":null,"abstract":"<p><strong>Background: </strong>Ethanol disrupts brain activity and memory. There is evidence supporting the beneficial effect of levetiracetam on alcohol consumption. Therefore, the aim of the study was to examine whether levetiracetam has a protective activity against ethanol-induced memory impairment, alterations in selected neurotransmission activities, oxidative stress, and selected essential elements in rats.</p><p><strong>Methods: </strong>The rats were given levetiracetam (300 mg/kg b.w. po) with ethanol for three weeks prior to behavioral tests. Spatial memory was tested using the Morris water maze, while recognition memory was evaluated using the Novel object recognition test. The GABA and glutamate concentration was determined in three rat brain regions (cerebellum, hippocampus, and cerebral cortex). Serum oxidative stress parameters and selected essential elements concentration (Cu, Mn, Zn, Fe, Mg) in the rat brain were analyzed.</p><p><strong>Results: </strong>Levetiracetam administered with ethanol improved spatial memory, but did not affect abstinence-induced impairment. The drug also decreased ethanol-induced long-term recognition memory impairment. No alterations in glutamate levels were observed. GABA levels were elevated by levetiracetam in the cerebral cortex and by ethanol in the cerebellum. Ethanol increased catalase activity (CAT) and decreased superoxide dismutase activity (SOD) in the serum. Levetiracetam significantly increased the activity of SOD. Alcohol disrupted the levels of trace elements (Mn, Zn, Mg) in the rat brain. Additionally, levetiracetam alone increased Mg, Fe, and Cu concentrations while all animals receiving the drug also had significantly lower concentrations of Zn.</p><p><strong>Conclusions: </strong>Levetiracetam had differential effects against ethanol-induced impairments. These findings could have important implications for future levetiracetam treatment in patients.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"1363-1376"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11582331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astaxanthin has a beneficial influence on pain-related symptoms and opioid-induced hyperalgesia in mice with diabetic neuropathy-evidence from behavioral studies.","authors":"Katarzyna Ciapała, Katarzyna Pawlik, Agata Ciechanowska, Wioletta Makuch, Joanna Mika","doi":"10.1007/s43440-024-00671-9","DOIUrl":"10.1007/s43440-024-00671-9","url":null,"abstract":"<p><strong>Background: </strong>The treatment of painful diabetic neuropathy is still a clinical problem. The aim of this study was to determine whether astaxanthin, a substance that inhibits mitogen-activated protein kinases, activates nuclear factor erythroid 2-related factor 2 and influences N-methyl-D-aspartate receptor, affects nociceptive transmission in mice with diabetic neuropathy.</p><p><strong>Methods: </strong>The studies were performed on streptozotocin-induced mouse diabetic neuropathic pain model. Single intrathecal and intraperitoneal administrations of astaxanthin at various doses were conducted in both males and females. Additionally, repeated twice-daily treatment with astaxanthin (25 mg/kg) and morphine (30 mg/kg) were performed. Hypersensitivity was evaluated with von Frey and cold plate tests.</p><p><strong>Results: </strong>This behavioral study provides the first evidence that in a mouse model of diabetic neuropathy, single injections of astaxanthin similarly reduce tactile and thermal hypersensitivity in both male and female mice, regardless of the route of administration. Moreover, repeated administration of astaxanthin slightly delays the development of morphine tolerance and significantly suppresses the occurrence of opioid-induced hyperalgesia, although it does not affect blood glucose levels, body weight, or motor coordination. Surprisingly, astaxanthin administered repeatedly produces a better analgesic effect when administered alone than in combination with morphine, and its potency becomes even more pronounced over time.</p><p><strong>Conclusions: </strong>These behavioral results provide a basis for further evaluation of the potential use of astaxanthin in the clinical treatment of diabetic neuropathy and suggest that the multidirectional action of this substance may have positive effects on relieving neuropathic pain in diabetes.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"1346-1362"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11582234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obesity-related drug transporter expression alterations in human liver and kidneys.","authors":"Katarzyna Kosicka-Noworzyń, Aleksandra Romaniuk-Drapała, Yi-Hua Sheng, Christine Yohn, Luigi Brunetti, Leonid Kagan","doi":"10.1007/s43440-024-00665-7","DOIUrl":"10.1007/s43440-024-00665-7","url":null,"abstract":"<p><strong>Background: </strong>Pathophysiological changes associated with obesity might impact various drug pharmacokinetics (PK) parameters. The liver and kidneys are the primary organs involved in drug clearance, and the function of hepatic and renal transporters is critical to efficient drug elimination (or reabsorption). Considering the impact of an increased BMI on the drug's PK is crucial in directing dosing decisions. Given the critical role of transporters in drug biodisposition, this study investigated how overweight and obesity affect the gene expression of renal and hepatic drug transporters.</p><p><strong>Methods: </strong>Human liver and kidney samples were collected post-mortem from 32 to 28 individuals, respectively, which were divided into the control group (lean subjects; 18.5 ≤ BMI < 25 kg/m²) and the study group (overweight/obese subjects; BMI ≥ 25 kg/m²). Real-time quantitative PCR was performed for the analysis of 84 drug transporters.</p><p><strong>Results: </strong>Our results show significant changes in the expression of genes involved in human transporters, both renal and hepatic. In liver tissue, we found that ABCC4 was up-regulated in overweight/obese subjects. In kidney tissue, up-regulation was only observed for ABCC10, while the other differentially expressed genes were down-regulated: ABCA1, ABCC3, and SLC15A1.</p><p><strong>Conclusions: </strong>The observed alterations may be reflected by the differences in drug PK between lean and obese populations. However, these findings need further evaluation through the proteomic and functional study of these transporters in this patient population.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"1429-1442"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11582170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"mGlu4R, mGlu7R, and mGlu8R allosteric modulation for treating acute and chronic neurodegenerative disorders.","authors":"Helena Domin, Grzegorz Burnat","doi":"10.1007/s43440-024-00657-7","DOIUrl":"10.1007/s43440-024-00657-7","url":null,"abstract":"<p><p>Neuroprotection, defined as safeguarding neurons from damage and death by inhibiting diverse pathological mechanisms, continues to be a promising approach for managing a range of central nervous system (CNS) disorders, including acute conditions such as ischemic stroke and traumatic brain injury (TBI) and chronic neurodegenerative diseases like Parkinson's disease (PD), Alzheimer's disease (AD), and multiple sclerosis (MS). These pathophysiological conditions involve excessive glutamatergic (Glu) transmission activity, which can lead to excitotoxicity. Inhibiting this excessive Glu transmission has been proposed as a potential therapeutic strategy for treating the CNS disorders mentioned. In particular, ligands of G protein-coupled receptors (GPCRs), including metabotropic glutamatergic receptors (mGluRs), have been recognized as promising options for inhibiting excessive Glu transmission. This review discusses the complex interactions of mGlu receptors with their subtypes, including the formation of homo- and heterodimers, which may vary in function and pharmacology depending on their protomer composition. Understanding these intricate details of mGlu receptor structure and function enhances researchers' ability to develop targeted pharmacological interventions, potentially offering new therapeutic avenues for neurological and psychiatric disorders. This review also summarizes the current knowledge of the neuroprotective potential of ligands targeting group III mGluRs in preclinical cellular (in vitro) and animal (in vivo) models of ischemic stroke, TBI, PD, AD, and MS. In recent years, experiments have shown that compounds, especially those activating mGlu4 or mGlu7 receptors, exhibit protective effects in experimental ischemia models. The discovery of allosteric ligands for specific mGluR subtypes has led to reports suggesting that group III mGluRs may be promising targets for neuroprotective therapy in PD (mGlu4R), TBI (mGlu7R), and MS (mGlu8R).</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"1219-1241"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11582148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}