imipramine / Generic mfg. - LARVOL DELTA

Topical Imipramine and Amitriptyline Block Experimental Ultraviolet B Radiation-induced Erythema in Rosacea Subjects (AAD 2026) - "Topical FIASMs amitriptyline and imipramine significantly reduced UVB-induced erythema in rosacea These studies provide premise for a novel therapeutic target for photosensitive rosacea."

Clinical • Dermatitis • Dermatology • Inflammation • Rosacea • MVP

Magnesium Transporter SLC41A1 Links Magnesium Homeostasis to NMDA Receptor-Related Synaptic Dysfunction: A Transdiagnostic Therapeutic Target for Neuropsychiatric Disorders. (PubMed, Biomedicines) - "Under NMDAR-selective recording conditions, both imipramine treatment and SLC41A1 knockdown significantly reduced NMDAR-mediated fEPSP amplitudes, supporting a role for SLC41A1 in regulating NMDA receptor-dependent synaptic responses. This study identifies SLC41A1 as a magnesium-centered, transdiagnostic therapeutic target that links Mg2+ homeostasis to NMDA-dependent synaptic dysfunction. These findings provide a mechanistic foundation for developing SLC41A1-modulating or magnesium-based therapeutic approaches for mood and cognitive disorders."

Journal • Addiction (Opioid and Alcohol) • Alzheimer's Disease • Bipolar Disorder • CNS Disorders • Cognitive Disorders • Depression • Developmental Disorders • Mental Retardation • Mood Disorders • Psychiatry

Cell line-specific antileukemic effects of imipramine: apoptosis, reactive oxygen species modulation and cytokine responses in human acute promyelocytic leukemia and chronic myelogenous leukemia cells. (PubMed, Mol Biol Rep) - No abstract available

Journal • Preclinical • Acute Promyelocytic Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Imipramine solubility-pH profiles: self-aggregation vs. common-ion effect. (PubMed, ADMET DMPK) - "The pH-dependent solubility of imipramine, a tricyclic antidepressant, and its hydrochloride salt was investigated in phosphate buffers and chloride-containing aqueous media using the pH-ramp shake-flask method. These findings, along with our previous solubility studies of desipramine and nortriptyline, suggest that even subtle structural variations can lead to significant differences in the aqueous media behaviour of tricyclic antidepressants. This type of information can be valuable in the early stages of drug discovery, in formulation optimization experiments, as well as in in vitro and in vivo studies."

Journal

Increased Cerebrospinal Fluid Lactate Levels in Schizophrenia and Major Depressive Disorder: NCNP Biobank Study in Japan. (PubMed, Neuropsychopharmacol Rep) - "This study confirmed elevated CSF lactate levels in Japanese individuals with schizophrenia and MDD, consistent with findings in other populations. The elevation of CSF lactate is unlikely to reflect medication effects and instead may represent an underlying pathophysiology associated with altered brain energy metabolism in the brain."

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

Clinical trial to evaluate the effectiveness and efficiency of a pre-emptive pharmacogenetic strategy for antidepressant selection in patients with depressive disorder: The PREDICT clinical trial. (clinicaltrialsregister.eu) - P4 | N=240 | Not yet recruiting | Sponsor: Fundacion Para La Investigacion Biomedica Del Hospital Universitario La Paz

Biomarker • New P4 trial • CNS Disorders • Depression • Mood Disorders • Psychiatry • HTR2A • SLC6A4

α-(Phenylselanyl) acetophenone reverses comorbid depressive-like behavior and mechanical allodynia induced by partial sciatic nerve ligation in mice. (PubMed, Behav Brain Res) - "Male Swiss mice underwent PSNL surgery, and after a four-week period, they received either PSAP (1-50mg/kg, administered intragastrically) or imipramine (IMI) (50mg/kg) 30minutes prior to behavioral assessments...Furthermore, PSAP restored hippocampal BDNF mRNA levels, which had been diminished by nerve injury. Since inflammation is a common pathway in both chronic pain and depression, the findings indicate that PSAP holds promise as a treatment for this comorbid condition."

Journal • Preclinical • CNS Disorders • Depression • Immunology • Inflammation • Pain • Psychiatry • BDNF • TNFA

Model-Based Steady State Pharmacokinetic Predictions Using High Throughput Cassette Infusion Approach in Mice. (PubMed, Xenobiotica) - "This study assessed the pharmacokinetics (PK) of Fulvestrant, Imipramine, and Brivaracetam using cassette dosing. All compounds reached steady-state within 24-36 hours, and clearance/exposure rankings were consistent across models and experiments. This integrated approach combining SC PK profiling, modeling, and cassette infusion enabled model-informed dose prediction and qualitative validation, which can support early PK evaluation and formulation development in drug discovery."

Journal • PK/PD data • Preclinical

Multi-lineage hepatic organoids reveal toxic exosome mediated indirect hepatotoxicity. (PubMed, Nat Commun) - "Consistently, imipramine long-term gavage in vivo triggers hepatic stellate cell apoptosis and toxic exosome-mediated hepatocyte injury without direct hepatocyte toxicity. Our findings establish a biomimetic organoid platform for precision drug testing and highlight the central role of intercellular communication in drug-induced liver injury."

Journal • Hepatology • Liver Failure • CASP3 • HNRNPA2B1 • MIR34A • NTRK2 • XIAP

Enuresis in Children. (PubMed, Indian J Pediatr) - "The mainstays of MNE treatment are an enuresis alarm and desmopressin...Imipramine is considered a third-line agent...Therapy-resistant and treatment-refractory enuresis should be diagnosed only after ensuring adherence to prescribed therapies. A range of alternative therapies may be explored and individualized based on the patient's needs."

Journal • Review • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Mental Retardation • Psychiatry • Sleep Disorder • Urinary Incontinence

Late-stage N-Me selective alkenylation and alkynylation of drugs and unactivated tertiary amines using photoredox catalysis. (PubMed, Nat Commun) - "Molecular modeling followed by bioactivity studies of novel imipramine alkenylated and alkynylated analogues shows improved efficiency compared to imipramine in reducing the depressive state, justifying the importance of N-methyl selective alkenylation and alkynylation. A thorough investigation of the reaction mechanism has been conducted to understand the regioselective formation of the N-Me selective product. DFT calculations combined with experimental evidence indicate that the regioselective outcome is controlled by the radical addition step not the radical formation step, which mostly remains unknown."

Journal • Depression

Antidepressant-Like Activity of Naringenin, an Important Agro-Industrial Resource, Complexed with β‑Cyclodextrin. (PubMed, ACS Omega) - "NR and NR-βCD, when administered acutely (20 and 40 mg/kg, p.o.), produced a significant reduction in the immobility time (p < 0.05), an effect comparable to imipramine (30 mg/kg, p.o.). The reduction in immobility time observed after NR treatment (20 mg/kg, p.o.) was prevented by pretreatment with haloperidol (0.2 mg/kg, i.p., a D2 receptor antagonist) and yohimbine (Yob) (1 mg/kg, i.p., an α2-adrenoceptor antagonist), but not with ondansetron (1 mg/kg, i.p., a 5-HT3 receptor antagonist). In summary, NR and NR-βCD produced an antidepressant-like effect with no change in locomotor activity. Furthermore, this anti-immobility effect seems to be mediated by interaction with dopaminergic and noradrenergic systems."

Journal

Electroacupuncture promotes BDNF-dependent neurogenesis via microglial reprogramming in a chronic stress model. (PubMed, Chin Med) - "Our findings demonstrate that EA exerts antidepressant effects by promoting a pro-neurogenic transformation of microglia. Mechanistically, these microglia enhance BDNF function via the PKA/MeCP2/BDNF pathway, thereby facilitating hippocampal neurogenesis and restoring synaptic plasticity, which collectively alleviate depressive symptoms."

Journal • CNS Disorders • Depression • Mood Disorders • Psychiatry • BDNF • NTRK2

Prefrontal cortex-extracellular vesicle RNAs coupling in alcohol use disorder: towards non-invasive biomarkers and targeted therapeutics. (PubMed, Artif Cells Nanomed Biotechnol) - "Computational drug repurposing identified loratadine, doxepin, citalopram and imipramine as promising therapeutic candidates targeting SERPINA3. Collectively, this work delineated PFC signature genes, proposed a EVs-supported brain-periphery molecular crosstalk, and provided translatable biomarkers and repurposable candidates for AUD precision medicine."

Biomarker • Journal • Addiction (Opioid and Alcohol) • IL17A • SERPINA3

Tricyclic Antidepressants as Prospective α-Synucleinopathy Fighters: Evidence of Protein Binding and Antiaggregation Activity. (PubMed, ACS Chem Neurosci) - "Here, we report the finding that clinically approved tricyclic antidepressants imipramine, amitriptyline, and doxepin bind directly to monomeric α-synuclein and inhibit its fibrillation, a key process in Parkinson's pathology...Moreover, simulations show that a single ligand molecule frequently engages in simultaneous salt-bridge and π-stacking interactions, unlike some previously studied α-synuclein binders. Our findings position tricyclic antidepressants as promising scaffolds for targeting α-synuclein and demonstrate the efficiency of molecular dynamics approaches for the description of interactions between small drug molecules and IDPs."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

Alleviation of depression rather than pain predicts disease improvement in fibromyalgia patients with prominent psychological symptoms-a prospective observational study. (PubMed, Semin Arthritis Rheum) - "Psychological symptoms, as much as pain, vitally determined disease severity in FM. For FM-AD individuals, alleviation of depression, rather than pain relief alone, pivotally predicted disease improvement. Early detecting and addressing depression in FM management could help with discriminating phenotypes, thereby improving FM care strategy."

Journal • Observational data • CNS Disorders • Depression • Fibromyalgia • Mood Disorders • Musculoskeletal Pain • Pain • Psychiatry • Rheumatology

Imipramine improves motor impairments in a rat model of Parkinson's disease induced by 6-hydroxydopamine; the role of oxidative stress and neurotrophic factors. (PubMed, Exp Neurol) - "These findings provide direct evidence that imipramine treatment contributes to improve of neuronal cell death and motor deficits, perhaps by increasing the striatal levels of SOD and GDNF, which play a key role in the survival of dopaminergic neurons. Further studies are also needed to elucidate the precise underlying molecular mechanisms of neuroprotective effects of imipramine."

Journal • Preclinical • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • BDNF

Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between CYP2D6 and CYP2C19 and tricyclic antidepressants. (PubMed, Eur J Hum Genet) - "For CYP2D6 poor metabolisers (PM), dose reductions are advised for amitriptyline (reduction to 60% of the normal dose), clomipramine (reduction to 50% of the normal dose for the indication depression or in case of side effects at the normal dose for the other indications), doxepin (reduction to 40% of normal dose), imipramine (30% of the normal dose), and nortriptyline (40%)...The DPWG classifies CYP2D6 genotyping for all five TCAs and CYP2C19 genotyping for clomipramine in patients with anxiety disorders or OCD, and for imipramine as being "potentially beneficial". Genotyping prior to treatment can be considered on an individual patient basis."

Biomarker • Journal • CNS Disorders • Depression • Mood Disorders • Obsessive-Compulsive Disorder • Psychiatry • CYP2C19

Mechanism of Antidepressant Drug Loading in Surface-Active Ionic Liquid: Insights from Micelle Morphology and Energy Analysis Using Coarse-Grained MD Simulations. (PubMed, J Phys Chem B) - "In the current study, a coarse-grained molecular dynamics (CG) simulation was carried out to investigate the mechanism of loading of an antidepressant drug, imipramine (IMP), with 1-decyl-3-methylimidazolium bromide (DMI) in aqueous medium at a concentration range...The IMP weakens the electrostatic repulsive interaction between DMI monomers. The strong synergistic interactions between the SAIL and drug molecules in the mixed micelles are attributed to the formation of cationic mixtures."

Journal

NS-398-induced membrane stiffening as a biophysical factor affecting memory-related processes. (PubMed, Biochem Biophys Res Commun) - "We found a more than tenfold increase in membrane stiffness and consistent changes in its compressibility. Our findings demonstrate that COX-2 inhibition increases cell membrane stiffness, implicating membrane mechanics as a novel link between biochemical signaling and cognitive functions."

Journal • CNS Disorders • Depression • Psychiatry

A new drug-drug co-amorphous system of imipramine and celecoxib with improved solubility and synergistic antinociceptive effects. (PubMed, Eur J Pharm Biopharm) - "Isobolographic analysis demonstrated that IMI-CEL (1:1) showed synergistic analgesic effects in paclitaxel-induced neuropathic pain in mice. Moreover, the oral bioavailability of 1:1 IMI-CEL was improved 1.396 times in rats when compared to the single drug. Above results suggested the potential of IMI-CEL to produce synergistic analgesic effects through developing drug-drug co-amorphous systems."

Journal • Neuralgia • Pain

Repositioning serotonergic antagonists as therapeutic agents in gastric cancer: induction of apoptosis, inhibition of cell migration, and cell cycle arrest in AGS cells. (PubMed, Cytotechnology) - "Imipramine induced G1/S phase arrest, whereas tropisetron, ketanserin, and cyproheptadine increased the sub-G1 cell population. Gene expression analysis revealed decreased Bcl-2 and PCNA levels and increased Bax expression.These findings suggest the potential of tropisetron, imipramine, ketanserin, and cyproheptadine as repurposed therapeutic agents for gastric cancer."

IO biomarker • Journal • CNS Disorders • Depression • Gastric Cancer • Oncology • Psychiatry • Solid Tumor • BAX • BCL2 • PCNA • SLC6A4

Effectiveness of Pharmacological Treatments for Adult ADHD on Psychiatric Comorbidity: A Systematic Review. (PubMed, J Clin Med) - "This systematic review evaluated the effectiveness of commonly prescribed medications for adult ADHD (methylphenidate, atomoxetine, bupropion, and lisdexamfetamine) on comorbid mood, anxiety, personality, and substance use disorders. Tricyclic antidepressants were also included in the search strategy; however, no eligible adult studies assessing imipramine or desipramine in patients with ADHD and psychiatric comorbidity were identified...While targeted improvements may occur in specific domains, the evidence base is insufficient to define optimal long-term strategies for adults with ADHD and complex comorbidity. Rigorous, longitudinal studies are needed to clarify medication effects on distinct comorbid profiles and to inform integrated treatment planning."

Journal • Review • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Mood Disorders • Personality Disorder • Psychiatry

Clinical behavior toward outpatients with major depressive disorder based on guideline education for psychiatrists. (PubMed, PCN Rep) - "The secondary outcomes were the imipramine equivalent dose of antidepressants and the diazepam equivalent dose of anxiolytics/hypnotics. In terms of the secondary outcomes, the diazepam equivalent dose was significantly lower in patients treated by psychiatrists who were participating in the EGUIDE project. Participation in the EGUIDE project was associated with improved severity diagnosis rates among outpatients with MDD, but its effect on prescribing behaviors was limited."

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

The Effect of Topical Imipramine on Photodynamic Therapy-Mediated Immunosuppression on Forearms or Face on US Veterans (clinicaltrials.gov) - P2 | N=48 | Recruiting | Sponsor: VA Office of Research and Development | N=24 ➔ 48

Enrollment change • Actinic Keratosis • Dermatology • Oncology • Squamous Cell Carcinoma