desipramine / Generic mfg. - LARVOL DELTA

Effects of Acute Ketamine and Chronic Desipramine on Brain Structure and Neurochemistry in a model of chronic stress in adolescent rats (Neuroscience 2025) - "MRS revealed that both treatments similarly elevated glutamate concentrations in the medial prefrontal cortex. However, T2-weighted imaging showed that only desipramine treatment significantly increased the volume of the left anterior cingulate cortex, suggesting distinct structural effects between the two antidepressants."

Preclinical • CNS Disorders • Depression • Psychiatry

The Investigation of the Mechanism of Action of Chloroquine Retinopathy: By prevention of lysosomal membrane permeabilization (LMP) (Neuroscience 2025) - "A total of three candidate protective drugs were selected, amiodarone, nortriptyline and desipramine, amiodarone was selected as the most effective against cell death measured by LDH release (amiodarone: 27.65 ± 5.56%, nortriptyline: 64.30 ± 7.73%, desipramine: 67.30 ± 9.36%). The identified compounds represent promising candidates for adjunct therapies to prevent vision loss in patients requiring long-term CQ treatment. Further validation in animal models and clinical studies is warranted to translate these protective effects into clinical practice."

CNS Disorders • CTSD

Experimental study on the treatment of norepinephrine transporter-overexpressing pheochromocytomas and paragangliomas: a synthetic lethality strategy combining 131I-MIBG with PARP inhibitors. (PubMed, Front Oncol) - "This study aims to investigate the therapeutic potential of 131I-MIBG and the PARP inhibitor fluzoparib monotherapies and their combination on two distinct PC12-derived stable cell lines: PC12-NET cells and PC12-NET-SDHB cells...The specificity of PC12-NET cells to the 131I-MIBG was confirmed through desipramine inhibition assays...The combined of 131I-MIBG with PARP inhibitor demonstrated a synergistic antitumor effect in PC12-NET cells. While PC12-NET-SDHB cells display comparable sensitivity to 131I-MIBG as PC12-NET cells, they exhibited heightened responsiveness to PARP inhibitor treatment."

Journal • Oncology • Solid Tumor • SDHB

Lysosomal Membrane Permeabilization Sensitizes Ctss-Hyperactive Tumors to BCL2-Targeting Therapies (ASH 2023) - "We next employed LMP-inducing tool compounds (LLOMe) and clinically used drugs or analogs (desipramine, hexamethylene amiloride) to release cathepsins into the cytosol...The combination of LLOMe-induced LMP and the BCL2 inhibitor venetoclax (VEN) showed increased cytotoxicity in CTSS-hyperactive Karpas422 cells compared to monotherapy and CSTB k/d enhanced this phenotype (Fig A, bottom)...In summary, we show that CSTB is a functionally relevant inhibitor that determines the net activity of LMP-released cytosolic CTSS. Furthermore, LMP-inducing therapies may be a promising approach to sensitize CTSS-hyperactive tumors towards apoptosis by proteolytic cleavage of BCL2 family members."

IO biomarker • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • BCL2 • BCL2L1 • CTSS • MCL1

The Differential Involvement of α1-Adrenoceptor Subtypes in the Molecular Effects of Antidepressant Drugs. (PubMed, Int J Mol Sci) - "We investigated whether the functional involvement of α1-adrenergic receptors (α1-AR) in the effects induced by antidepressant drugs, desipramine, and milnacipran varies depending on the α1-AR subtype. The pattern of changes differed by gender. Our study revealed the functional diversity between α1-AR subtypes in the molecular mechanisms of antidepressants' drug action."

Journal • GSK3B

Comparing Effectiveness of Duloxetine and Desipramine in Patients With Chronic Pain: A Pragmatic Trial Using Point of Care Randomization (clinicaltrials.gov) - P4 | N=86 | Completed | Sponsor: Stanford University | Recruiting ➔ Completed | N=320 ➔ 86

Enrollment change • Trial completion • Pain

Deciphering the structural impact of norepinephrine analog radiopharmaceuticals on organic cation transporter affinity. (PubMed, Biomed Pharmacother) - "This study highlights the critical influence of the compounds' chemical structure on NET and OCT affinities. Structural modifications that reduce OCT-mediated uptake while maintaining high NET affinity could improve the specificity and theranostic potential of NET-targeting ligands. These findings provide insights for designing next-generation radiotracers with enhanced selectivity and clinical utility."

Journal • Neuroendocrine Tumor • Oncology • Solid Tumor • SLC22A1 • SLC22A2

Druggable Genome Mendelian Randomization and GWAS-sceQTLs MR Analysis Reveal Genetic Associations Between Open-Angle Glaucoma and Immune Cells, and Identify Potential Drugs. (PubMed, Transl Vis Sci Technol) - "(3) Drug screening: Molecular docking confirmed strong binding of trimipramine, desipramine, and cyclosporin to GFPT1 (Vina score < -5), with PheWAS indicating no significant off-target effects. Three existing drugs identify potential for therapeutic repurposing. This study identifies GFPT1-driven immunometabolic dysfunction as a novel target in POAG and nominates three US Food and Drug Administration (FDA)-approved drugs for immediate clinical translation, accelerating the path to trials."

Journal • Glaucoma • Metabolic Disorders • Ophthalmology • CD4 • KLRB1 • YWHAG

Assessing Cytochrome P450 Drug Interaction Risk for Dordaviprone Using Physiologically Based Pharmacokinetic Modeling. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "The simulated increase in dordaviprone AUC and Cmax (4.6- and 1.7-fold) following administration of multiple doses of itraconazole was consistent with the observed values (4.4- and 1.9-fold). All PBPK-simulated changes in dordaviprone plasma exposure when administered with CYP3A4 moderate (erythromycin, fluconazole) and weak (cimetidine) inhibitors, and moderate (efavirenz) and strong (rifampicin) inducers were consistent with their CYP3A4 potency classification (AUC ratio = 2.68, 2.48, 1.42, 0.35, and 0.17, respectively). The simulated AUC and Cmax of probe substrates for CYP3A4 (midazolam), CYP2C8 (repaglinide) and CYP2D6 (desipramine) after coadministration with 625 mg dordaviprone were the same as those in the absence of dordaviprone (ratio = 1.0) and remained unchanged after a sensitivity analysis using 10-fold more potent inhibition constants. Due to changes in dordaviprone plasma exposure when co-administered with CYP3A4 inhibitors, dordaviprone dose adjustments..."

Journal • PK/PD data • Brain Cancer • Glioma • Oncology • Solid Tumor

The Missing Link: Connecting Cultivation Conditions and Refolding Performance via Inclusion Body Biophysical Properties. (PubMed, Biotechnol Bioeng) - "Using a design of experiments approach, this study systematically explored how cultivation conditions-postinduction temperature, pH, and feed rate-affect the production of IBs containing anti-desipramine single-chain variable fragment antibodies as a model therapeutic protein...Higher protein content in the IBs adversely affected the refolding yield due to a hidden coupling between cultivation and refolding. This study establishes IB biophysical properties as critical factors for linking upstream and refolding process performance, offering actionable insights to enhance bioprocess robustness and efficiency."

Journal

Sulfonatocalixarene Promotes Drug Assembly Based on Supramolecular Host•-Guest Complexation in Aqueous Solution. (PubMed, Chem Asian J) - "Supramolecular nano-sized assemblies with high structural stability are designed based on hostguest complexation in aqueous solution using sulfonatocalix[n]arenes (SXCn) as macrocyclic hosts and three drug molecules (doxepin, desipramine, and promazine)...Despite the high-water solubility of SCX4 and the drug molecules, their combination reveals the formation of supramolecular assembly at low millimolar concentrations. These assemblies exhibit a thermoresponsive behavior, highlighting their potential for the design of functional materials."

Journal

Machine learning-based model for behavioural analysis in rodents applied to the forced swim test. (PubMed, Sci Rep) - "Our ML model was validated against manual scoring in rats treated with fluoxetine and desipramine, two antidepressants known to induce distinct behavioural patterns...Subsequently, we successfully validated our model by testing its ability to distinguish between drugs that predominantly evoke climbing (i.e., amitriptyline), those that preferentially facilitate swimming (i.e., paroxetine), and those that evoke both in a more balanced manner (i.e., venlafaxine). This approach represents a significant advancement in preclinical research, providing a more accurate and efficient method to analyze forced swimming data in rodents. We anticipate that in addition to the FST, our model and approach could be extended for application to various behavioural tests in laboratory animals, by training with specific datasets."

Journal • Preclinical

Preclinical Developments of Novel Theranostic Radiopharmaceutical 3-[76Br/77Br]bromo-pHPG (SNMMI 2025) - "In particular, parahydroxyphenethylguanidine (pHPG) is a suitable norepinephrine-transporter- (NET-) targeted vector with two advantages over the more studied benzylguanidine ([131I]mIBG): faster localization in adrenergic tumor and higher tumor retention...Total and non-specific (blocked with 10 µM desipramine) binding experiments tested cell uptake kinetics from 0.07–100 nM 3-[natBr]Br-pHPG... In vitro 50% effective concentrations (EC50) for SK-N-SH were 7.9 nM (0.48 MBq/mL, n=6) with 95% confidence interval (CI95%) of 5.0 – 14 nM for 3-[77Br]Br-pHPG and 1.29 mM (CI95%= 1.18 – 1.42 mM, n=4) for 3-natBr-pHPG. Similarly, the EC50 for SK-N-MC and SK-N-Be(2)-C were 140 nM (4.6 MBq/mL, CI95%=113 – 149 nM, n=1) and 7.3 nM (1.7 MBq/mL, CI95%=6.3 – undefined nM, n=1), respectively (Figure 2a). Minimal difference was observed between total and non-specific 3-[77Br]Br-pHPG binding to SK-N-SH cells."

Preclinical • Neuroblastoma • Oncology • Solid Tumor

Tricyclic antidepressants dose-dependently modulate the biphasic activity of the TRPC5 channel through opioid receptors. (PubMed, Korean J Physiol Pharmacol) - "Without altering TRPC5 expression levels, TCAs (amitriptyline, desipramine, and imipramine) dose-dependently reduced inward currents through TRPC5, with IC₅₀ values of 2.9, 10.3, and 11.7 μM, respectively. The biphasic modulation of TRPC5 by TCAs may contribute to a wide spectrum of cardiovascular and neurological manifestations, depending on the dosage and clinical application. Overall, these findings enhance the pharmacological understanding of the molecular mechanisms underlying the actions of TCAs and emphasize the need for more targeted therapeutic approaches."

Journal • Addiction (Opioid and Alcohol) • Cardiovascular • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • TRPC5

Pharmacological inhibition of acid sphingomyelinase reduces stasis-induced thrombus formation (ISTH 2025) - "The results are as follow: thrombus weight- control group, 33.5±5.0 mg; Imipramine-treated, 18.65±3.4 mg; Amitriptyline-treated, 17.03±4.0 mg; Desipramine-treated, 16.32±3.6 mg¦ thrombus length- control group, 6.78±1.28 mm; Imipramine-treated, 4.7±1.7 mm; Amitriptyline-treated, 3.6±2.14 mm; Desipramine-treated, 2.71±1.7 mm). No significant differences were found in thrombus weight or length between animals treated with SMS2 inhibitor (thrombus weight 29.23±3.88 mg; length 4.85±1.7 mm) and control vehicle."

Cardiovascular • Hematological Disorders • Thrombosis

Dissecting the pro-neurogenic effects of monoaminergic medications used to treat depression: a systematic review and meta-analysis. (PubMed, J Psychopharmacol) - "The available number of studies was also insufficient to yield definitive evidence for compounds acting as selective serotonin reuptake inhibitors (citalopram, escitalopram, fluvoxamine), serotonin-norepinephrine reuptake inhibitors (desvenlafaxine, duloxetine, venlafaxine), multimodal monoaminergic modulators (imipramine, desipramine), melatonergic compound (agomelatine), or norepinephrine-serotonin disinhibitory (mirtazapine). Subsequent updates of these reviews appear necessary to establish robust evidence regarding these compounds. Evidence was firm in favor of a robust pro-neurogenic effect of selective serotonin reuptake inhibitor fluoxetine, in both species, making updates of this review probably redundant."

Journal • Retrospective data • Review • CNS Disorders • Depression • Mood Disorders • Psychiatry

An Overview of the Systematic Reviews About the Efficacy of Fluvoxamine on Depression. (PubMed, Pharmaceuticals (Basel)) - "Comparisons with imipramine, clomipramine, amitriptyline, dothiepin, paroxetine, fluoxetine, citalopram, mianserin, nortriptyline, and moclobemide generally revealed no significant differences in efficacy. However, some reviews indicated that venlafaxine and mirtazapine were superior to fluvoxamine in certain outcomes, while fluvoxamine demonstrated greater efficacy than desipramine in one review. Sertraline and milnacipran showed mixed or review-quality-dependent results, with one low-quality review favoring milnacipran...While no single antidepressant was universally superior, fluvoxamine's unique pharmacological profile and favourable safety characteristics support its clinical utility. Further research is needed to explore its role in personalized treatment strategies and emerging therapeutic contexts, such as comorbid anxiety and post-traumatic stress disorder."

Journal • Review • CNS Disorders • Depression • Mental Retardation • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry

EVALUATING THE SAFETY OF PHARMACOTHERAPY FOR IRRITABLE BOWEL SYNDROME: A META-ANALYSIS (DDW 2025) - "AEs were more varied for tricyclics (indicated for IBS global symptoms); for example, compared to placebo the three most common AEs with associated risk increases were drowsiness (14%), dry mouth (12%), and weight gain (9%) for amitriptyline, dry mouth (22%), flushing (18%), and constipation (17%) for desipramine, and fatigue (15%), dry mouth (3%) and blurry vision (1.5%) for doxepin...The NNH for linaclotide, lubiprostone, plecanatide, tegaserod, and tenapanor (indicated for IBS-C) was 27 (p < 0.01), 53 (p = 0.59), 58 (p < 0.01), 59 (p = 0.03), and 17 (p <0.01) respectively. The NNH for alosetron and eluxadoline (indicated for IBS-D) was 16 (p < 0.01) and 32 (p < 0.01). Ramosetron and rifaximin (indicated for IBS-D) had a negative risk difference, with the rate of withdrawal due to AEs higher in the placebo arm, so NNH was a negative, although statistically insignificant, value... Tricyclics, alosetron, and tenapanor are associated with a higher..."

Retrospective data • Constipation • Fatigue • Gastrointestinal Disorder • Xerostomia

SELECTIVE SEROTONIN REUPTAKE INHIBITORS AND TRICYCLIC ANTIDEPRESSANTS USE IN INFLAMMATORY BOWEL DISEASE PATIENTS MAY BE ASSOCIATED WITH POOR CLINICAL OUTCOMES (DDW 2025) - "Subjects were stratified into groups using commonly prescribed selective serotonin reuptake inhibitors (SSRI) (fluoxetine, citalopram, escitalopram, paroxetine, sertraline), tricyclic antidepressants (TCA) (amitriptyline, doxepin, imipramine, nortriptyline, desipramine), or monoamine oxidase inhibitors (MAOI) (selegiline, isocarboxazid, phenelzine, tranylcypromine) for at least one year. Herein we showed that SSRI and TCA use in IBD patients is associated with poor clinical outcomes in terms of requiring steroid therapy, hospitalization, and death. Some studies have suggested that this may be due to SSRI-induced dysbiosis which may lead to gut inflammation. MAOI use was not associated with statistically significant worsened outcomes however this may be due to insufficient power."

Clinical • Clinical data • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Pain • Psychiatry • Ulcerative Colitis

Dysfunction of subthalamic dopaminergic circuitry contributes to anxiety- and depression-like behaviors in 6-OHDA lesion-induced hemiparkinsonian mice. (PubMed, Acta Pharmacol Sin) - "A hemi-parkinsonian mouse model was established by injection of 6-OHDA into the right medial forebrain bundle (MFB), desipramine (20 mg/kg, i.p.) was injected 30 min before the intracranial injection...Intracranial injection of either D1- or D2-like dopamine receptor agonist into the STN mitigated anxiety- and depression-like behaviors in the parkinsonian mice. We conclude that STN DA circuitry may be promising targets to treat anxiety and depression in PD."

Journal • Preclinical • CNS Disorders • Depression • Mood Disorders • Movement Disorders • Parkinson's Disease • Psychiatry

Carbon Materials in Voltammetry: An Overview of Versatile Platforms for Antidepressant Drug Detection. (PubMed, Micromachines (Basel)) - "Moreover, the combination of voltammetric approaches with the unique characteristics of carbon and its derivatives has led to the development of powerful electrochemical sensing tools for detecting antidepressant drugs, which are highly desirable in healthcare, environmental monitoring, and the pharmaceutical industry. In this review, carbon-based materials, such as glassy carbon and boron-doped diamond, and a wide spectrum of carbon nanoparticles, including graphene, graphene oxides, reduced graphene oxides, single-walled carbon nanotubes, and multi-walled carbon nanotubes were described in terms of the sensing performance of agomelatine, alprazolam, amitriptyline, aripiprazole, carbamazepine, citalopram, clomipramine, clozapine, clonazepam, desipramine, desvenlafaxine, doxepin, duloxetine, flunitrazepam, fluoxetine, fluvoxamine, imipramine, nifedipine, olanzapine, opipramol, paroxetine, quetiapine, serotonin, sertraline, sulpiride, thioridazine, trazodone, venlafaxine,..."

Journal • Review • CNS Disorders • Depression • Mood Disorders • Personality Disorder • Psychiatry

Intrauterine Exposure to Psychotropic Medications as a Risk Factor for Neonatal Opioid Withdrawal Syndrome (PAS 2025) - "Those with exposure to psychotropic medication were more likely to also have exposure to other substances (i.e., alcohol, nicotine, marijuana, and methamphetamine) (84% vs. 69%; p< 0.05; Table 1). Of the 1,305 infants included in the ESC-NOW study, 297 (22.8%) had antenatal co-exposure to psychotropic medications. The mean length of stay was 1.6 days longer for infants with psychotropic exposure compared to those without exposure (12.1 vs. 10.5 days, respectively; p < 0.001) (Table 2)."

Clinical • Addiction (Opioid and Alcohol) • Substance Abuse

Efficacy and tolerability of antidepressants in individuals suffering from physical conditions and depressive disorders: network meta-analysis. (PubMed, Br J Psychiatry) - "Antidepressants are effective in individuals with comorbid physical conditions, although tolerability is a relevant concern. Selective serotonin reuptake inhibitors (SSRIs) have the best benefit-risk profile, making them suitable as first-line treatments, while tricyclics are highly effective but less tolerated than SSRIs and placebo."

Journal • Retrospective data • Review • CNS Disorders • Depression • Mood Disorders • Psychiatry

Influence of antidepressant use on periodontal status: a systematic review and meta-analysis. (PubMed, Clin Oral Investig) - "This study informs health professionals that certain antidepressants may positively impact the periodontium, while also highlighting the need for further research evaluating their possible influence on the human periodontal condition and their potentially associated local/systemic adverse effects."

Clinical • Journal • Retrospective data • Review • Dental Disorders • Inflammation • Osteoporosis • Periodontitis

In vitro-in vivo scaling of cytochrome P450-mediated metabolic clearance using a relative activity factor approach. (PubMed, Drug Metab Dispos) - "We selected multiple probe substrates for CYP1A2 (caffeine, tizanidine, phenacetin), CYP2C9 ((S)-acenocoumarol, glimepiride, lornoxicam, tolbutamide, (S)-warfarin), CYP2C19 ((S)-lansoprazole, omeprazole, pantoprazole), CYP2D6 (desipramine, metoprolol, nebivolol, tolterodine), and CYP3A4 (alprazolam, felodipine, midazolam, nisoldipine, sildenafil, triazolam) to calculate the representative RAF value for each P450 isoform based on the in vivo-to-in vitro clearance ratio of the multiple probe substrates...The fm values of the responsible P450 isoform(s) could be well predicted for mexiletine, tamsulosin, risperidone, celecoxib, and glibenclamide...By applying relative activity factor values obtained from multiple probe substrates, this study was able to quantitatively predict the in vivo clearances mediated by CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. This simple, practical method will help optimize metabolic clearances via the major cytochrome P450..."

Journal • Preclinical • CYP1A2 • CYP2C19 • CYP2C9 • CYP3A4