imipramine / Generic mfg. - LARVOL DELTA

Application of acoustic ejection mass spectrometry for plasma protein binding assay using flux dialysis. (PubMed, Drug Metab Dispos) - "Herein, we validated this approach using 10 commercially available compounds with known fu values-imipramine, indomethacin, itraconazole, lapatinib, nicardipine, warfarin, chlorpromazine, rivastigmine, zonisamide, and ritonavir-with a wide fu range covering from very high binding (fu ≤ 0.01) to low binding (fu > 0.10) in human plasma. SIGNIFICANCE STATEMENT: This study bridges the gap between flux dialysis and acoustic ejection mass spectrometry by creating a synergistic analytical framework for plasma protein binding assays, addressing limitations of both methods and enabling high-throughput applications with improved accuracy and efficiency. The combination of flux dialysis and acoustic ejection mass spectrometry will make a positive contribution to the development of high-throughput in vitro absorption, distribution, metabolism and excretion assays in drug discovery."

Journal

Antidepressant-like Effects of Garcinia nigrolineata Resin Extract in a Chronic Mild Stress Mouse Model: Modulation of Monoaminergic and HPA-Axis Pathways. (PubMed, Plants (Basel)) - "The resin extract of Garcinia nigrolineata (GNR-E), a tropical plant used in Southeast Asian traditional medicine, was evaluated for its antidepressant-like effects in a chronic mild stress (CMS) mouse model, with imipramine as a reference drug...Phytochemical analysis identified xanthones, particularly cowanin, as key constituents. These findings highlight GNR-E's potential as a novel plant-based antidepressant, warranting further investigation into its active compounds and clinical applications."

Journal • Preclinical • CNS Disorders • Depression • Psychiatry

The impact of antidepressant use on antibiotic treatment outcomes in urinary tract infections and pneumonia: A population-based cohort study. (PubMed, Psychiatry Clin Neurosci) - "Antidepressants are associated with a modest rise in UTI treatment failure risk, possibly due to antibiotic resistance or other mechanisms. Despite this, their essential role in mental health management outweighs the small risk, emphasizing the need for judicious use, particularly in females and older adults. Further research is warranted to clarify underlying mechanisms."

Journal • Infectious Disease • Nephrology • Pneumonia • Respiratory Diseases

Discovery of a Novel and Potent Kir4.1 Inhibitor as a Safe and Rapid-Onset Antidepressant Agent in Mice. (PubMed, Adv Sci (Weinh)) - "Notably, a single administration of JX3212 results in rapid-onset antidepressant effects within 1 h in multiple rodent models of depression, with comparable efficacy to (S)-ketamine; this inhibitor-like effect is abolished in mice with tamoxifen-induced conditional Kir4.1 knockout in astrocytes. Additionally, JX3212 demonstrates superior safety margins compared to both (S)-ketamine and the conventional antidepressant imipramine in murine behavioral assays. In summary, JX3212 functions as a selective Kir4.1 inhibitor with favorable druggability and stable antidepressant efficacy in preclinical models. This pharmacological profile supports the further development of JX3212 as a promising therapeutic candidate for major depressive disorder."

Journal • Preclinical • CNS Disorders • Depression • Major Depressive Disorder • Mental Retardation • Mood Disorders • Psychiatry

Characterization and Prognostic Impact of Fascin Expression in the Tumor Microenvironment of Triple-Negative Breast Cancer: Clues for a Tailored Therapy. (PubMed, Lab Invest) - "These findings highlight the dual role of fascin in tumor cells and the tumor microenvironment (TME), and reinforce its potential as a biomarker for personalized TNBC therapies. Ongoing clinical trials, including HITCLIF, are exploring the efficacy of imipramine in patients with fascin-overexpressing cancers, paving the way for targeted treatment strategies."

Biomarker • IO biomarker • Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BCL2 • Fascin • FSCN1 • HER-2

Possible involvement of keratinocyte-derived microvesicle particles in human photosensitivity disorders. (PubMed, Photochem Photobiol) - "Moreover, post-UVB application of imipramine blunted UVB-induced MVP responses as well as tended to diminish erythema levels at 4 h but not at 24 or 72 h in photosensitive patients. Though limited by low numbers of self-identified subjects, these pilot studies provide some support for the hypothesis that MVP could be involved in multiple types of human photosensitivity responses and suggest aSMase inhibition as a potential therapeutic strategy."

Journal • Dermatology • MVP

Possible involvement of keratinocyte-derived microvesicle particles in human photosensitivity disorders. (PubMed, medRxiv) - "Moreover, post-UVB application of imipramine blunted UVB-induced MVP responses as well as tended to diminish erythema levels at 4 h but not at 24- or 72 h in photosensitive patients. Though limited by low numbers of self-identified subjects, these pilot studies provide some support for the hypothesis that MVP could be involved in multiple types of human photosensitivity responses and suggest aSMase inhibition as a potential therapeutic strategy."

Journal • Dermatology • MVP

The Administration of Melatonin Improved Depressive Behavior in Both Maximal Electroshock Seizure-Prone and Non-Seizure Mice After Undergoing Levetiracetam Treatment. (PubMed, Turk J Pharm Sci) - "The results observed with melatonin were similar to those of imipramine. Melatonin was found to reduce depressive behavior in both non-epileptic and epileptic groups. These results suggest that melatonin could be a potential therapeutic agent for countering the depressive effects of levetiracetam."

Journal • Preclinical • CNS Disorders • Depression • Epilepsy • Mental Retardation • Psychiatry

Restoring mitochondria-endoplasmic reticulum-synapse axis: a proteomic dissection of Rhein's multi-pathway antidepressant mechanism. (PubMed, Biochem Pharmacol) - "Using quantitative proteomics on prefrontal cortex samples from control, CSDS, Rhein-treated, and imipramine-treated cohorts, we identified differentially expressed proteins that revealed Rhein's multi-target regulatory profile...We inferred that this organelle-centered regulation further reinforces its potent modulation through multiple mechanisms and signaling pathways of synaptic plasticity, enabling Rhein to exert antidepressant effects through a coordinated, multi-layered mechanism. Collectively, our findings provide a systems-level mechanistic framework for Rhein's antidepressant efficacy and support its potential as a multi-pathway natural therapeutic, particularly for metabolic subtypes of depression."

Journal • CNS Disorders • Depression • Mental Retardation • Metabolic Disorders • Psychiatry • HDAC1

An open-source, budget-friendly tail suspension test platform with high temporal resolution for behavioral and neural correlation studies (Neuroscience 2025) - "As a proof of concept, we tested the effects of the antidepressant imipramine (15 mg/kg, i.p.), which significantly reduced immobility compared to saline controls (p<0.0001, n=8 for each group). In summary, our automated TST platform enables efficient, high-throughput behavioral assessment with minimal experimenter bias. All hardware schematics, firmware, and analysis code will be freely available to the neuroscience community."

CNS Disorders • Mood Disorders • Pain

Preventing relapse in patients with major depressive disorder after an effective acute course of electroconvulsive therapy. (PubMed, Australas Psychiatry) - "Imipramine, phenelzine, amitriptyline and CBT demonstrated encouraging results, while escitalopram failed to show a favourable outcome. Clinicians aiming to reduce the risk of relapse after an effective acute course of ECT could consider lithium, nortriptyline, venlafaxine and CBT."

Journal • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Laser Secondary Neutral Mass Spectrometry of Bi3+ Sputtered Pharmaceuticals. (PubMed, Anal Chem) - "In this work, Laser-SNMS has been studied for six pharmaceuticals, including carbamazepine, verapamil, imipramine, ciprofloxacin, tetracycline and rifampicin. By varying the laser power density and the delay between the primary ion impact and the laser pulse, photofragmentation patterns that could be used for unambiguous compound identification were discovered. The ion yield was notably enhanced over ToF-SIMS for the molecular ion or large fragment ions for all of the compounds investigated."

Journal

Sorafenib generates microvesicle particles in non-small cell lung cancer. (PubMed, Tumor Discov) - "Moreover, co-treatment with imipramine enhanced the cytotoxic effects of sorafenib, suggesting that targeting MVP-associated pathways may improve sorafenib response. Collectively, these findings offer mechanistic insight into how sorafenib modulates MVP release and supports the therapeutic potential of combining tyrosine kinase inhibitors with agents that disrupt MVP biogenesis in NSCLC."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MVP

Lysosome dysfunction alters intestinal morphology and lipid metabolism in early neonatal piglets. (PubMed, BMC Vet Res) - "These results demonstrate that lysosome dysfunction induced by imipramine resulted in significant growth retardation, pronounced morphological and ultrastructural alterations in ileal enterocytes, along with disrupted lipid metabolism in early postnatal piglets; however, no such effect was observed in 27-day-old piglets. These findings enhance understanding of lysosomal functions and intestinal maturation in neonatal piglets."

Journal • Gastrointestinal Disorder • Metabolic Disorders • APOA1 • APOB

NORADRENERGIC AND NITRIC OXIDE MODULATORS INFLUENCE ANTIDEPRESSANT EFFECTS OF AGOMELATINE IN MICE (WCN 2025) - "Agomelatine (40 mg/kg), imipramine (10 mg/kg, a tricyclic antidepressant), bupropion (10 mg/kg, dopamine /norepinephrine-reuptake inhibitor), prazosin (1 mg/kg, an α1-adrenoceptor antagonist), yohimbine (1 mg/kg, an α2-adrenoceptor antagonist), and propranolol (2 mg/kg, a β-adrenoceptor antagonist), L-arginine (100 mg/kg, NO precursor), L-NAME (10 mg/kg, NO synthetase inhibitor), methylene blue (5mg/kg, guanylate cyclase inhibitor) were injected 30 min before administration of agomelatine, α-methyl-p-tyrosine (100 mg/kg, an inhibitor of tyrosine hydroxylase) was administered 3 h before agomelatine. Agomelatine proved potential antidepressant effects, that was enhanced by adrenergic or nitric oxide pathway modulation. Further research is warranted to determine the precise molecular mechanisms and optimize clinical applications."

Preclinical • CNS Disorders • Depression • Psychiatry

Contribution of particle-induced lysosome membrane permeabilization to NLRP3 inflammasome activation and mitochondrial ROS production. (PubMed, Toxicol Sci) - "Imipramine was used to inhibit LMP before measuring mtROS and NLRP3 inflammasome activation and MitoTEMPO was used to block mtROS before measuring LMP and NLRP3 inflammasome activation...The inability of MitoTEMPO to block the effects of Ni2+ ions on mtROS production suggested an alternative unclear mechanism was involved. This study demonstrates that LMP serves as a pivotal upstream trigger of NLRP3 inflammasome activation and potentially ROS production in response to cSiO2 and NiONPs-underscoring the crucial role of lysosomes in particle-induced inflammation."

Journal • Inflammation • Pneumonia • NLRP3

Inflammatory biomarkers and antidepressant response: towards personalised treatment (ECNP 2025) - "For example, tricyclic antidepressants such as clomipramine and imipramine, as well as the SSRI citalopram, have been shown to inhibit the release of pro-inflammatory cytokines including IL-6, IL-1β, and TNF-α in human monocytes. [2] In contrast, some studies have reported that patients with elevated CRP levels may respond better to antidepressants that target the noradrenergic or dopaminergic systems, such as venlafaxine or bupropion. Moreover, adjunctive treatment with anti-inflammatory agents, including nonsteroidal anti-inflammatory drugs (NSAIDs) and minocycline, has been associated with enhanced antidepressant efficacy in patients with elevated inflammatory biomarkers... Inflammatory biomarkers, particularly CRP and IL-6, show considerable promise as predictors of antidepressant response in MDD. Personalizing antidepressant therapy based on baseline inflammatory profiles may allow for more targeted treatments, improving patient outcomes and reducing the time spent..."

Biomarker • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • CRP • IL1B • IL6 • TNFA

Targeting the resolution of inflammation to improve the treatment of depression (ECNP 2025) - "Male Flinders Sensitive Line (FSL) rats, a validated model of gene × environment-driven low-grade inflammation and depression, were treated with vehicle, ketamine (15 mg/kg, i.p.), or imipramine (15 or 30 mg/kg, i.p.), either acutely or for seven consecutive days. These findings support that dysregulation of resolution-related signaling—particularly involving AnxA1, FPR2, and GILZ—contributes to depressive-like behavior and influences treatment response. These pathways may represent promising targets for improving antidepressant efficacy."

CNS Disorders • Depression • Mood Disorders • Psychiatry • ANXA1 • FPR2

LIVER INJURY DUE TO MEDICATIONS FOR MENTAL HEALTH: AN ANALYSIS OF THE DRUG-INDUCED LIVER INJURY NETWORK PROSPECTIVE STUDY (AASLD 2025) - "Bupropion (6 cases) and imipramine (1 cases) were the only agents of their respective classes (aminoketone and tricyclic antidepressant). Despite frequent use, the frequency of DILI cases due to antidepressants and APs in the US is low, and most cases showed rapid improvement. However, severe cases leading to chronic DILI or death rarely occur. It is important for practitioners to keep in mind the rare possibility of DILI as an adverse effect of these agents."

Clinical • CNS Disorders • Hepatology • Liver Failure

Imipramine-Induced Catatonia in a Patient With Primary Nocturnal Enuresis and Emerging Bipolar Affective Disorder. (PubMed, Prim Care Companion CNS Disord) - No abstract available

Journal • Bipolar Disorder • CNS Disorders • Urinary Incontinence

Unmasking Hypnic Headache After Withdrawal from Medication Overuse: Two Case Reports (IHC 2025) - "Methods Case 1: A 68-year-old male developed daily headaches around age 50 and used diclofenac and ergotamine/caffeine three to four times daily for 15 years...He failed flunarizine (1 month), topiramate (2 months), and a single dose of fremanezumab...Previous preventive treatments (propranolol and imipramine) were ineffective...Preventive therapy plays a key role. Without it, reliance on acute medications may lead to recurrent medication overuse headache."

Case report • Clinical • CNS Disorders • Migraine

The Future of Oncology in Psychiatric Medications. (PubMed, J Clin Med) - "The anticancer potential of psychiatric drugs seems to be extremely broad, and the most extensive anticancer literature has been reported on antidepressants (fluoxetine, amitriptyline, imipramine, mirtazapine, and St John's Wort) and antipsychotics (chlorpromazine, pimozide, thioridazine, and trifluoperazine)...Among antidementia drugs, memantine has documented anticancer effects, while there is limited evidence for galantamine. Of the new psychiatric substances, the antipsychotic drug brexpiprazole and the antidepressant vortioxetine have a very interesting body of literature regarding glioblastoma, based on in vitro and in vivo animal survival studies...The anticancer properties of psychiatric drugs may prove particularly useful in the period between chemotherapy and radiotherapy sessions to maintain the tumor-inhibitory effect. While further research is necessary to elucidate the mechanisms, clinical implications, dose-dependence of the effect, and clear..."

Journal • Brain Cancer • CNS Disorders • Depression • Glioblastoma • Oncology • Psychiatry • Solid Tumor • BCL2 • CDKN1A • SIRT1

Kai-Xin-San Has Antidepressant-Like Effect in Tricyclic Antidepressant Treatment Resistant Animal Model by Rebalancing Tryptophan Metabolism. (PubMed, Chin J Integr Med) - "The therapeutic potential of KXS, especially combined with IMI, for TRD owed to its safeguarding effects on TRP metabolism. Pachymic acid, ginsenoside Rg1 and tenuifolin may be the primary contributors to these protective impacts of KXS."

Journal • Preclinical • CNS Disorders • Depression • Inflammation • Psychiatry • TDO2

Macropinocytosis inhibition attenuates pro-fibrotic responses in lung fibroblasts and pulmonary fibrosis. (PubMed, bioRxiv) - "The inhibition of macropinocytosis with 5-(n-ethyl-n-isopropyl)-amiloride (EIPA) significantly inhibited profibrotic responses in IPF-derived and TGF-β1-stimulated HLFs...Both genetic and pharmacological inhibition of macropinocytosis significantly ameliorated pulmonary fibrosis in bleomycin (Bleo)-injured mice...Finally, we found that imipramine (Imi), a tricyclic antidepressant approved by the Food and Drug Administration (FDA), effectively inhibited macropinocytosis and ameliorated profibrotic responses in lung fibroblasts, Bleo-injured mice and IPF-derived PCLS. Taken together, our results suggest macropinocytosis inhibition as a potential therapeutic strategy to treat pulmonary fibrosis."

Journal • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • MEOX1 • TGFB1

Imipramine Inhibits Osteosarcoma Invasion via Src Inactivation and Caspase-Dependent Apoptosis. (PubMed, J Cell Mol Med) - "Imipramine exerts potent anti-OS effects by suppressing Src-mediated invasion and enhancing caspase-dependent apoptosis through extrinsic and intrinsic pathways. It inhibits tumour progression without inducing systemic toxicity, demonstrating its potential as a therapeutic candidate for OS."

IO biomarker • Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • BCL2 • CASP3 • CASP8 • CASP9 • MCL1 • SNAI2 • XIAP