Hyperium (rilmenidine) / Servier - LARVOL DELTA

Rilmenidine attenuates intracerebral hemorrhage by regulating autophagy flux and apoptosis via the HO-1/Fe2+/ERK pathway. (PubMed, Neuroscience) - "RIL may play an antiapoptotic role by promoting autophagic degradation, promoting neuronal survival and restoring neural function. The results of this study provide a deeper understanding of the dynamic process of autophagy after ICH, and help to further reveal the mechanism secondary injury in ICH and to develop new therapeutic targets."

Journal • Cerebral Hemorrhage • Hematological Disorders • HMOX1

Not first-line antihypertensive agents, but still effective-The efficacy and safety of imidazoline receptor agonists: A network meta-analysis. (PubMed, Pharmacol Res Perspect) - "Moreover, moxonidine reduced blood pressure more effectively than enalapril; however, this difference was not significant (SBP MD: 3.10; 95% CI: -2.60-8.80; DBP MD: 1.30; 95% CI: -1.25-3.85)...After 8 weeks of treatment, the appearance of dry mouth was highest with clonidine (OR: 9.27 95% CI: 4.70-18.29) and lowest with rilmenidine (OR: 6.46 95% CI: 0.85-49.13) compared to placebo...However, in the case of resistant hypertension, they are a viable option. According to our findings, from the point of view of safety and efficacy, moxonidine appears to be the best choice among imidazoline receptor agonists."

Clinical • Journal • Retrospective data • Cardiovascular • Hypertension • Nephrology • Renal Disease • Xerostomia

Analysis of the nischarin expression across human tumor types reveals its context-dependent role and a potential as a target for drug repurposing in oncology. (PubMed, PLoS One) - "In concordance with the findings that nischarin expression was negatively associated with pathways that control cancer growth and progression, nischarin agonist rilmenidine decreased the viability of cancer cells in vitro. Taken together, our study lays a ground for functional studies of nischarin in a context-dependent manner and, given that nischarin has several clinically approved agonists, provides rationale for their repurposing, at least in tumors in which nischarin is predicted to be a positive prognostic marker."

Biomarker • Journal • Breast Cancer • Lung Cancer • Melanoma • Oncology • Ovarian Cancer • Solid Tumor

Synthesis of rilmenidine analogues as potential therapeutic agents for the treatment of breast cancer | Poster Board #1612 (ACS-Sp 2024) - "To this end the synthesis of a broad series of rilmenidine analogues has been initiated to establish the structure activity relationships of this molecule relative to Nischarin activation. To achieve the preparation of the initial target compounds, new chemistry has been explored for the efficient synthesis of the N-(2- chloroethyl)urea precursors to the target amino-oxazoline analogues."

Breast Cancer • Oncology • Solid Tumor

MELANOMA AND DYSPLASTIC NEVI DEVELOPMENT AFTER RANITIDINE/RILMENIDINE/МOXONIDINE, LERCANIDIPINE, ROSUVASTATIN AND VERAPAMIL/TRANDOLAPRIL - NEW DATA/CASE SERIES. THE POTENTIAL ROLE OF NITROSAMINE/NDSRIS CONTAMINATION IN POLYMEDICATION AS SUBSTANTIAL SKIN CANCER TRIGGERING FACTOR. (PubMed, Georgian Med News) - "In the last decade, melanoma has been described repeatedly in the medical literature as a possible side-effect within the intake of possibly with nitrosamines contaminated medications such as: Valsartan, Hydrochlorothiazide, Amlodipine, Nebivolol, Bisoprolol and Perindopril. Ingredients that are present in drug preparations, identified as availability and as carcinogenic potency, but not yet reflected in packaging or prescriptions. The question remains: why?"

Journal • Cutaneous Melanoma • Genetic Disorders • Melanoma • Oncology • Skin Cancer • Solid Tumor

New anti-aging strategies: a narrative review. (PubMed, Acta Dermatovenerol Alp Pannonica Adriat) - "Calorie restriction mimetics include the activator of AMP-activated protein kinase (metformin) and inhibitor of mTOR (rapamycin), alongside rilmenidine, exhibiting both effects. Age-related protein crosslinks are acknowledged as a causative factor in age-related diseases. Anti-aging medicine is an evolving field with a multitude of drugs and strategies, necessitating further clinical studies and long-term follow-up based on clinical experience and insights gained from delayed adverse events."

Journal • Review • Aesthetic Medicine • Cardiovascular • CNS Disorders • Diabetes • Metabolic Disorders • Oncology

Autophagy and anti-inflammation ameliorate diabetic neuropathy with Rilmenidine. (PubMed, Acta Cir Bras) - "The findings of this study suggest that Rilmenidine may have therapeutic effects on DNP by modulating antioxidant and autophagic pathways."

Journal • Diabetes • Diabetic Neuropathy • Fibrosis • Immunology • Inflammation • Metabolic Disorders • Oncology • Pain • NGF • TNFA

Comprehensive analysis of candidate signatures of long non-coding RNA LINC01116 and related protein-coding genes in patients with hepatocellular carcinoma. (PubMed, BMC Gastroenterol) - "Differentially expressed LINC01116 could be a candidate diagnostic and an independent prognostic signature in HCC. Besides, its target drugs may work for HCC therapy via the VEGF receptor signaling pathway. Differentially expressed OLFML2B could be a diagnostic signature involved in HCC via immune infiltrates."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • LINC01116 • OLFML2B • PLAU • TMSB15A

Preclinical validation of rilmenidine for repurposing in pancreatic ductal adenocarcinoma (EACR 2023) - "Ultimately, in the ex vivopatient tissues treatment with rilmenidine remodeled extracellular matrix.ConclusionTaken together, nischarin agonist rilmenidine reduces PDAC cancer cell invasion in vitro and in vivo and has an impact on cancer-stroma interactions. Our study lays a ground for potential repurposing of antihypertensive drug rilmenidine as antimetastatic therapeutic in PDAC."

IO biomarker • Preclinical • Cardiovascular • Gastrointestinal Cancer • Hepatology • Hypertension • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • FLI1

Blood Pressure Reduction Induced by Chronic Intracerebroventricular or Peroral Clonidine Administration inRats with Salt-Dependent or Angiotensin II-Dependent Hypertension. (PubMed, Physiol Res) - "Basal BP and the contributions of renin-angiotensin system (captopril 10 mg/kg iv) or sympathetic nervous system (pentolinium 5 mg/kg iv) to BP maintenance were determined in conscious cannulated rats at the end of the study. In contrast, peroral clonidine treatment reduced angiotensin II-dependent vasoconstriction in Ren-2 transgenic rats, whereas it lowered residual blood pressure in Dahl rats. In conclusions, our results indicate different mechanisms of antihypertensive action of clonidine when administered centrally or systemically."

Journal • Cardiovascular • Hypertension • Hypotension

Nischarin receptor agonist rilmenidine decreases production of pro-tumorigenic cytokines and growth factors in pancreatic ductal adenocarcinoma stellate cells (EACR 2022) - "Our results imply that rilmenidine, an FDA-approved drug for the treatment of hypertension, decreases the production of pro-tumorigenic factors in PDAC stellate cells. These results lay a ground for further examination of rilmenidine potential for drug repurposing in PDAC."

Cardiovascular • Hypertension • Oncology • Ovarian Cancer • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CAFs • CCL2 • CXCL8 • FAP • FN1 • IL10 • IL6

Data-driven methodology for discovery and response to pulmonary symptomology in hypertension through statistical learning and data mining: Application to COVID-19 related pharmacovigilance. (PubMed, Elife) - " Following multiple filtering stages to exclude insignificant and noise-driven reports, we found that drugs from antihypertensives agents, urologicals, and antithrombotic agents (macitentan, bosentan, epoprostenol, selexipag, sildenafil, tadalafil, and beraprost) form a similar class with a significantly higher incidence of pADEs...Nifedipine and candesartan were also found by signal detection methods to form a drug cluster, shown by several studies an effective combination of these drugs on lowering blood pressure and appeared an improved side effect profile in comparison with single-agent monotherapy...For instance, macitentan and bosentan from endothelin receptor antagonists show major concern while doxazosin and rilmenidine exhibited the least pADEs compared to the outcomes of other drugs. Using techniques in this study, we assessed and confirmed the hypothesis that drugs from the same drug class could have very different pADE profiles affecting outcomes in acute..."

Adverse events • Clinical • Journal • Hypertension • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Urology

The Role of Autophagy in Chemical Proteasome Inhibition Model of Retinal Degeneration. (PubMed, Int J Mol Sci) - "These results suggest that Becn1-mediated autophagy is not an effective intrinsic protective mechanism for retinal damage induced by insults, including impaired proteasomal activity; furthermore, autophagic activation beyond normal levels is required to alleviate the cytotoxic effect of proteasomal inhibition. Further studies are underway to delineate the precise roles of different forms of autophagy, and investigate the effects of their activation in rescuing retinal neurons under various pathological conditions."

Journal • Neuroblastoma • Oncology • Solid Tumor • Targeted Protein Degradation • BECN1 • mTOR

[VIRTUAL] Nischarin as a target for drug repurposing in solid tumors (EACR 2021) - "NISCH has several clinically approved agonists that are used for treatment of hypertension (rilmenidine, clonidine, moxonidine) that have been shown to modulate autophagy, reduce inflammation and fibrosis. Conclusion NISCH is potentially a good candidate as a target for drug repurposing in solid tumors. Our future efforts will include validation of NISCH prognostic role in solid tumors and extensive preclinical examination of the mechanisms by which NISCH agonists exert their anticancer properties."

Breast Cancer • Colorectal Cancer • Diabetes • Fibrosis • Gastrointestinal Cancer • Hypertension • Immunology • Inflammation • Melanoma • Metabolic Disorders • Oncology • Pancreatic Cancer • Solid Tumor

[VIRTUAL] Nischarin as a target for drug repurposing in solid tumors (EACR 2021) - "NISCH has several clinically approved agonists that are used for treatment of hypertension (rilmenidine, clonidine, moxonidine) that have been shown to modulate autophagy, reduce inflammation and fibrosis. Conclusion NISCH is potentially a good candidate as a target for drug repurposing in solid tumors. Our future efforts will include validation of NISCH prognostic role in solid tumors and extensive preclinical examination of the mechanisms by which NISCH agonists exert their anticancer properties."

Breast Cancer • Colorectal Cancer • Diabetes • Fibrosis • Gastrointestinal Cancer • Hypertension • Immunology • Inflammation • Melanoma • Metabolic Disorders • Oncology • Pancreatic Cancer • Solid Tumor

[VIRTUAL] Nischarin as a target for drug repurposing in solid tumors (EACR 2021) - "NISCH has several clinically approved agonists that are used for treatment of hypertension (rilmenidine, clonidine, moxonidine) that have been shown to modulate autophagy, reduce inflammation and fibrosis. Conclusion NISCH is potentially a good candidate as a target for drug repurposing in solid tumors. Our future efforts will include validation of NISCH prognostic role in solid tumors and extensive preclinical examination of the mechanisms by which NISCH agonists exert their anticancer properties."

Breast Cancer • Colorectal Cancer • Diabetes • Fibrosis • Gastrointestinal Cancer • Hypertension • Immunology • Inflammation • Melanoma • Metabolic Disorders • Oncology • Pancreatic Cancer • Solid Tumor

[VIRTUAL] Nischarin as a target for drug repurposing in solid tumors (EACR 2021) - "NISCH has several clinically approved agonists that are used for treatment of hypertension (rilmenidine, clonidine, moxonidine) that have been shown to modulate autophagy, reduce inflammation and fibrosis. Conclusion NISCH is potentially a good candidate as a target for drug repurposing in solid tumors. Our future efforts will include validation of NISCH prognostic role in solid tumors and extensive preclinical examination of the mechanisms by which NISCH agonists exert their anticancer properties."

Breast Cancer • Colorectal Cancer • Diabetes • Fibrosis • Gastrointestinal Cancer • Hypertension • Immunology • Inflammation • Melanoma • Metabolic Disorders • Oncology • Pancreatic Cancer • Solid Tumor

Stimulation of mTOR-independent autophagy and mitophagy by rilmenidine exacerbates the phenotype of transgenic TDP-43 mice. (PubMed, Neurobiol Dis) - "These results suggest that autophagy induction accelerates the phenotype of this TDP-43 mouse model of ALS, most likely through excessive mitochondrial clearance in motor neurons. These findings also emphasise the importance of balancing autophagy stimulation with the potential negative consequences of hyperactive mitophagy in ALS and other neurodegenerative diseases."

Journal • Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders • Complement-mediated Rare Disorders • TARDBP

Development and Validation of Two New Methods for the Determination of Rilmenidine in Bulk and Pharmaceutical Preparation. (PubMed, J Chromatogr Sci) - "Detection limits for the spectrofluorimetric and HPLC methods were calculated as 0.16 and 18.28 ng/mL, respectively. The validated methods were applied successfully to the determination of rilmenidine in bulk and pharmaceutical preparation."

Journal

Centrally acting antihypertensives change the psychogenic cardiovascular reactivity. (PubMed, Fundam Clin Pharmacol) - "Altogether, both antihypertensives relieved the psychogenic cardiovascular responses to different stimuli. The RI elicited higher cardioprotective effects through a reduction in air-jet induced tachycardia."

Journal • Cardiovascular • Hypertension

Imidazoline Receptor System: The Past, the Present, and the Future. (PubMed, Pharmacol Rev) - "Existing data suggest that I receptors may represent a binding site at the Kir6.2-subtype ATP-sensitive potassium channels in pancreatic β-cells and may be involved in insulin secretion. Despite the elusive nature of their molecular identities, recent progress on drug discovery targeting imidazoline receptors (I and I) demonstrates the exciting potential of these compounds to elicit neuroprotection and to treat various disorders such as hypertension, metabolic syndrome, and chronic pain."

Journal • Review • Hypertension • Metabolic Disorders • Pain

Identification of potential prognostic small nucleolar RNA biomarkers for predicting overall survival in patients with sarcoma. (PubMed, Cancer Med) - "Our study have identified 15 snoRNAs that may be serve as novel prognostic biomarkers for sarcoma, and constructed a prognostic signature based on four prognostic snoRNA expression values."

Biomarker • Clinical • Journal • Oncology • Sarcoma • Solid Tumor • RB1

Autophagy in neurodegeneration: New insights underpinning therapy for neurological diseases. (PubMed, J Neurochem) - "We summarize studies pinpointing mitophagy mediated by the serine/threonine kinase PINK1 and the ubiquitin-protein ligase Parkin as a mechanism potentially relevant to Parkinson's disease, despite debate over the physiological conditions in which it is activated in organisms. Finally, with the example of the autophagy-inducing agent rilmenidine and its discrepant effects in cell culture and mouse models of motor neuron disorders, we illustrate the importance of considering aspects such a disease stage and aggressiveness, type of insult and load of damaged or toxic cellular components, when choosing the appropriate drug, timepoint and duration of treatment."

Journal • Review • CNS Disorders • Gene Therapies • Movement Disorders • Parkinson's Disease • Targeted Protein Degradation • Vascular Neurology

Cardiovascular Effects Mediated by Imidazoline Drugs: an Update. (PubMed, Cardiovasc Hematol Disord Drug Targets) - "Currently, new imidazoline receptors ligands are in development. In the present review, we provide a brief update on the cardiovascular effects of clonidine, moxonidine, rilmenidine, and the novel imidazoline agents since representing an important therapeutic target for some cardiovascular diseases."

Journal • Brain Cancer • Cardiovascular • CNS Disorders • Depression

Mitochondrial dysfunction is associated with long-term cognitive impairment in an animal sepsis model. (PubMed, Clin Sci (Lond)) - "Long-term impairment of brain function is temporally related to mitochondrial dysfunction. Activators of autophagy and mitochondrial biogenesis could rescue animals from cognitive impairment."

Journal • Preclinical • Alzheimer's Disease • Infectious Disease • Septic Shock