dihydroergocristine / Generic mfg. - LARVOL DELTA

Perturbation response scanning of drug-target networks: Drug repurposing for multiple sclerosis. (PubMed, J Pharm Anal) - "Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of serotonin 2B receptor (HTR2B)...These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS. As a useful systematic method, our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases."

Journal • CNS Disorders • Multiple Sclerosis • HTR2B

Identification of neuronal synapse-related signatures and potential therapeutic drugs in colorectal cancer based on machine learning algorithms and molecular docking. (PubMed, Transl Cancer Res) - "Drug prediction and molecular docking suggested alprostadil, dihydroergocristine, and nocodazole as candidate drugs for CRC treatment. This is the first study to develop neuron synapse-related biomarkers from the perspective of neuron-cancer interactions using machine learning. We constructed a robust NSRS model and identified candidate drugs targeting prognostic NSGs, providing new insights into CRC prognosis and treatment."

Journal • Colorectal Cancer • Oncology • Solid Tumor

A Genetic Perspective to Reveal the Impact of Mitochondrial Dysfunction-related Genes on Diabetic Kidney Disease: A Multi-omics Study. (PubMed, Curr Med Chem) - "This study suggests that ACTN1 may be a therapeutic target for DKD and sheds light on its molecular pathogenesis, clinical prevention, and treatment."

Journal • Diabetic Nephropathy • Inflammation • Metabolic Disorders • Nephrology • Renal Disease • CCNB1 • TUBA1A

Proteostasis regulation of GABAA receptors in neuronal function and disease. (PubMed, Biomed Pharmacother) - "This review summarizes recent progress about how the proteostasis network regulates protein folding, assembly, degradation, trafficking, and synaptic clustering of GABAARs. Additionally, emerging pharmacological approaches that restore proteostasis of pathogenic GABAAR variants are presented, providing a promising strategy to treat related neurological diseases."

Journal • Review • CNS Disorders • Developmental Disorders • Epilepsy • Mental Retardation • Psychiatry

Untangling the complex mechanisms associated with Alzheimer's disease in elderly patients using high-throughput RNA sequencing data and next-generation knowledge discovery methods: Focus on potential gene signatures and drugs for dementia. (PubMed, Heliyon) - "Several drugs and natural products, including dihydroergocristine, mepacrine, gedunin, amlodipine, and disulfiram have been identified as potential therapeutic agents for reversing AD-associated gene signatures. These findings highlight the complex molecular mechanisms underlying AD and provide insights into potential therapeutic strategies. Further research is needed to validate these findings and to develop personalized treatment approaches for AD in elderly patients."

Gene Signature • Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Geriatric Disorders • SUZ12

Effects of Gamma Irradiation on Changes in Chemical Composition and Antioxidant Activity of Euphorbia maculata Callus. (PubMed, Plants (Basel)) - "These findings suggest that gamma irradiation induces specific biochemical modifications that enhance the bioactive properties of PC3012 calli. This technology exhibits potential for utilization in the natural product and food sectors, particularly in the development of functional foods and nutraceuticals with improved health benefits."

Journal

Molecular docking based comparative study of antiviral compounds on SARS-CoV-2 spike protein. (PubMed, Nat Prod Res) - "Using molecular docking and the Lipinski five rule, this study illustrates possible compounds with strong binding affinities, their molecular interactions, for both naturally occurring and man-made drugs. Computational approach is applied, and it is concluded that, drugs like Withanolide, Dihydroergocristine, Fenebrutinib, and Ergotamine shows binding energies between -8.3 and -9.1 kcal/mol, and are possible candidate for anti covid drug."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Targeting aberrant glycosylation to modulate microglial response and improve cognition in models of Alzheimer's disease. (PubMed, Pharmacol Res) - "Furthermore, we found that an increase in bisecting GlcNAc modified ICAM-1 resulted in impairment of microglial responses, and genetic inactivation of GnT-III protected against AD mechanistically by blocking the aberrant glycosylation of ICAM-1 and subsequently modulating microglial responses, including microglial motility, phagocytosis ability, homeostatic/reactive state and neuroinflammation. Moreover, by target-based screening of GnT-III inhibitors from FDA-approved drug library, we identified two compounds, regorafenib and dihydroergocristine mesylate, showing pharmacological potential leading to modulation of aberrant glycosylation and microglial responses, and rescue of memory and cognition deficits."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Inflammation • ICAM1 • TCF7 • TCF7L2

DHEC mesylate attenuates pathologies and aberrant bisecting N-glycosylation in Alzheimer's disease models. (PubMed, Neuropharmacology) - "Evidence suggests that dihydroergocristine (DHEC) mesylate, one of the main components of Ergoloid mesylates, can reduce the production of amyloid-β in vitro...We further explored the underlying mechanism and confirmed that DHEC mesylate protected against AD via AMPK and ERK signaling, in which, AMPK was the dominant down-stream molecule of DHEC mesylate. In summary, our findings provide foundations for development of DHEC mesylate as a therapeutic approach for AD."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

Targeting PDE4A for therapeutic potential: exploiting drug repurposing approach through virtual screening and molecular dynamics. (PubMed, J Biomol Struct Dyn) - "In conclusion, our study systematically explores repurposing existing FDA-approved drugs as PDE4A inhibitors through a comprehensive virtual screening pipeline. The identified compounds, Fluspirilene and Dihydroergocristine, exhibit a strong affinity for PDE4A, displaying characteristics that support their suitability for further development as potential therapeutic agents for conditions associated with PDE4A dysfunction.Communicated by Ramaswamy H. Sarma."

Journal • Alzheimer's Disease • Asthma • Chronic Obstructive Pulmonary Disease • CNS Disorders • Depression • Immunology • Mood Disorders • Movement Disorders • Oncology • Parkinson's Disease • Psychiatry • Pulmonary Disease • Respiratory Diseases

Identifying repurposed drugs as potential inhibitors of Apolipoprotein E: A bioinformatics approach to target complex diseases associated with lipid metabolism and neurodegeneration. (PubMed, Int J Biol Macromol) - "In particular, Ergotamine and Dihydroergocristine emerge as noteworthy candidates, binding to ApoE in a competitive mode. This intriguing binding behavior positions these compounds as potential candidates warranting further analysis in the pursuit of novel therapeutics targeting complex diseases associated with lipid metabolism and neurodegeneration. This approach holds the promise of catalyzing advancements in therapeutic intervention for complex disorders, thereby reporting a meaningful pace towards improved healthcare outcomes."

Journal • CNS Disorders • Metabolic Disorders • APOE

Antinociceptive effects of nefopam activating descending serotonergic modulation via 5-HT2 receptors in the nucleus raphe magnus. (PubMed, Eur J Pain) - "This study revealed supraspinal mechanisms of nefopam-produced analgesia mediated by 5-HT2 receptors in the NRM recruiting the descending serotonergic fibres to increase the release of 5-HT into the spinal dorsal horn. These observations support a potential role for nefopam in multimodal analgesia based on its distinct mechanisms of action that are not shared by the other analgesics."

Journal • Pain

Identification of Potential Treatments for Acute Lymphoblastic Leukemia through Integrated Genomic Network Analysis. (PubMed, Pharmaceuticals (Basel)) - "Based on potentially druggable genes that we identified, palbociclib, sirolimus, and tacrolimus were under clinical trial for ALL. Additionally, chlorprothixene, sirolimus, dihydroergocristine, papaverine, and tamoxifen are the top five drug repositioning candidates for ALL according to the CMap score with dasatinib as a comparator. In conclusion, this study determines the practicability and the potential of integrated genomic network analysis in driving drug discovery in ALL."

Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • ARID5B

A computer-aided drug design approach to discover tumour suppressor p53 protein activators for colorectal cancer therapy. (PubMed, Bioorg Med Chem) - "The most promising according to the limits established above was dihydroergocristine. This compound revealed cytotoxic activity against a p53-expressing CRC cell line with an IC of 56.8 µM. This study demonstrated that the computer-aided drug design approach can be used to identify previously unknown molecules for targeting p53 protein with anti-cancer activity and thus pave the way for the study of a therapeutic solution for CRC."

Journal • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Cleaving Ergot Alkaloids by Hydrazinolysis-A Promising Approach for a Sum Parameter Screening Method. (PubMed, Toxins (Basel)) - "In this study, two promising cleaving methods-acidic esterification and hydrazinolysis-are compared, using dihydroergocristine as a model compound...Application of hydrazinolysis to a major ergot alkaloid mix solution showed that all ergopeptines were cleaved, but ergometrine/-inine was barely affected. Still, hydrazinolysis is a suitable tool for the development of a sum parameter screening method for ergot alkaloids in food and feed."

Journal

Systemically administered neurotensin receptor agonist produces antinociception through activation of spinally projecting serotonergic neurons in the rostral ventromedial medulla. (PubMed, Korean J Pain) - "Direct injection of PD 149163 into the RVM mimicked the maximum effect of the same drug delivered intraperitoneally, which was reversed by intrathecal dihydroergocristine. These observations indicate that systemically administered NTSR1 agonist produces antinociception through the NTSR1 in the RVM, activating descending serotonergic projection to release 5-HT into the spinal dorsal horn."

Journal • Neuralgia • Pain • Peripheral Neuropathic Pain

In Vitro Effect and Mechanism of Action of Ergot Alkaloid Dihydroergocristine in Chemoresistant Prostate Cancer Cells. (PubMed, Anticancer Res) - "DHECS has the potential to be repurposed as a novel anticancer agent for the management of chemoresistant PCa."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Dementia • Genito-urinary Cancer • Hematological Malignancies • Leukemia • Oncology • Prostate Cancer • Retinal Disorders • Solid Tumor

Antiallodynic Effect of Intrathecal Korean Red Ginseng in Cisplatin-Induced Neuropathic Pain Rats. (PubMed, Pharmacology) - "Intrathecally administered KRG decreased CINP. In addition, spinal 5-HT7 receptors contributed to the antiallodynic effect of KRG."

Journal • Preclinical • Neuralgia • Pain • Peripheral Neuropathic Pain

Antinociceptive role of neurotensin receptor 1 in rats with chemotherapy-induced peripheral neuropathy. (PubMed, Korean J Pain) - "CIPN was induced by injecting cisplatin (2 mg/kg) once a day for 4 days...Intrathecal administration of dihydroergocristine, a serotonin receptor antagonist, suppressed the antinociceptive effect of intrathecally administered, but not intraperitoneally administered, PD 149163...Therefore, NTSR1 agonists may be useful therapeutic agents to treat CIPN. In addition, spinal serotonin receptors may be indirectly involved in the effect of NTSR1 agonist."

Journal • Preclinical • Neuralgia • Oncology • Pain • Peripheral Neuropathic Pain

Proteostasis Regulators Restore Function of Epilepsy-Associated GABA Receptors. (PubMed, Cell Chem Biol) - "We screened a structurally diverse, Food and Drug Administration-approved drug library and identified dinoprost (DNP) and dihydroergocristine (DHEC) as highly efficacious enhancers of surface expression of four epilepsy-causing trafficking-deficient mutant receptors...Mechanistic studies revealed that both drugs reduce subunit degradation by attenuating the Grp94/Hrd1/Sel1L/VCP-mediated ERAD pathway and enhance the subunit folding by promoting subunit interactions with major GABA receptors-interacting chaperones, BiP and calnexin. In summary, we report that DNP and DHEC remodel the endoplasmic reticulum proteostasis network to restore the functional surface expression of mutant GABA receptors."

Journal • CNS Disorders • Epilepsy

Antinociceptive effects of nefopam modulating serotonergic, adrenergic, and glutamatergic neurotransmission in the spinal cord. (PubMed, Neurosci Lett) - "In another cohorts of animals, dihydroergocristine, yohimbine, or (RS)-α-Methylserine-O-phosphate (MSOP), a serotonergic, α-2 adrenergic receptor, or group III metabotropic glutamate receptor antagonist, respectively, were administered prior to the application of nefopam in the formalin test. The microdialysis results revealed that intrathecal nefopam significantly increased 5-HT and NE levels and attenuated the formalin-induced release of glutamate in the spinal cord. Thus, the present data suggest that the increase in the extracellular levels of 5-HT and NE, and reductions in glutamate release in the spinal cord, may have contributed to the analgesic effects of nefopam."

Journal • Pain

Neural coding: time contraction and dilation in the striatum. (PubMed) - "How the brain encodes time is poorly understood. New research on rats provides evidence that striatal neurons encode time, and that the code can dilate or contract to time different intervals."

Journal • Biosimilar

Selective Thalamic Innervation of Rat Frontal Cortical Neurons. (PubMed) - "The basal dendrites of L2/3b pyramidal and L5b corticopontine pyramidal cells received cortical and thalamic glutamatergic inputs in proportion to their local abundance, whereas crossed-corticostriatal pyramidal cells in L5b exhibited a preference for thalamic inputs, particularly in their distal dendrites. Our data demonstrate an exquisite selectivity among thalamocortical afferents in which synaptic connectivity is dependent on the postsynaptic neuron subtype, cortical sublayer, and cell surface domain."

Journal • Biosimilar

The dopamine theory of addiction: 40 years of highs and lows. (PubMed) - "Moreover, there is good evidence that striatal dopamine receptor availability and dopamine release are diminished in individuals with stimulant or alcohol dependence but not in individuals with opiate, nicotine or cannabis dependence. These observations have implications for understanding reward and treatment responses in various addictions."

Journal • Biosimilar

Network topology and functional connectivity disturbances precede the onset of Huntington's disease. (PubMed) - "Both analytic approaches provided a unique window into brain reorganization that was not related to brain atrophy or motor symptoms. Longitudinal studies currently in progress will chart the course of functional changes to determine the most sensitive markers of disease progression."

Journal • Biosimilar