desipramine / Generic mfg. - LARVOL DELTA

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

NMDA receptor antagonism requires serotonin and noradrenaline to induce antidepressant-like effects in a treatment-resistant depression rat model. (PubMed, Eur J Pharmacol) - "Thus, independent groups of Wistar Kyoto Rats were administered MK-801 alone or with desipramine or sertraline, and then evaluated in the open field and the forced swimming test (FST). In conclusion, MK-801 may enhance the effect of classical antidepressants in treatment-resistant models. Moreover, NMDA receptor antagonism relies on the integrity of the serotonergic and noradrenergic systems to exert antidepressant-like effects."

Journal • Preclinical • CNS Disorders • Depression • Mood Disorders • Psychiatry

Subacute ivermectin-induced affective dysregulation: Evidence for hippocampal microglial and astrocytic activation. (PubMed, Res Vet Sci) - "Assay validation employed diazepam (1 and 3 mg/kg; i.p.), desipramine (30 mg/kg; i.p.), and piracetam (200 mg/kg; i.p.), administered according to their respective protocols. Collectively, our data indicate that subacute, high-dose IVR provokes affective behavioural alterations coupled to hippocampal neuroinflammation, while sparing gross motor function and measurable cognitive performance under the present conditions. These findings underscore caution when administering IVR at elevated doses or in settings that compromise BBB integrity and warrant further mechanistic and time-resolved investigation."

Journal • CNS Disorders • Depression • Inflammation • Mood Disorders • Psychiatry • ABCB1 • GFAP

Irritable Bowel Syndrome (IBS) Functional Magnetic Resonance Imaging (fMRI) With Desipramine (clinicaltrials.gov) - P=N/A | N=18 | Terminated | Sponsor: Washington University School of Medicine | N=70 ➔ 18 | Completed ➔ Terminated; Due to changes in trial personnel (co-investigator and research coordinator leaving the institution).

Enrollment change • Trial termination • Gastrointestinal Disorder • Pain

Effects of Kamikihito on the Noradrenergic System and Its Pharmacokinetic Profile. (PubMed, Biol Pharm Bull) - "In addition, in the tail suspension test, KKT shortened the duration of immobility posture, indicative of behavioral despair, in lipopolysaccharide-injected mice, similar to desipramine, a NAT inhibitor...Geniposide and formononetin were identified and puerarin, gardoside, 3',7-dihydroxy-4'-methoxyisoflavone 7-O-glucoside, and kazonol N were estimated as ingredients that distribute both in the blood and brain. Although these ingredients did not exhibit NAT inhibitory activity, the information presented in this pharmacokinetic study will be a valuable resource for future studies on the molecular mechanisms of KKT action."

Journal • PK/PD data • CNS Disorders • Mood Disorders • Psychiatry

A Comprehensive Approach to the Antidepressant-like Effect and Toxicity of Thunbergia alata Bojer ex Sims (Acanthaceae): Involvement of the Serotoninergic System. (PubMed, Pharmaceuticals (Basel)) - " The extract significantly reduced the immobility time of mice in both the TST and the FST, without affecting locomotor activity, as did the prototypical antidepressant desipramine. PCPA, AMPT, and NAN-190 abolished the extract's effects on despair, while serotonergic ligands (8-OH-DPAT, fluoxetine, and pindolol) facilitated their antidepressant action... This is the first study to demonstrate that an aqueous extract of T. alata produces antidepressant effects mediated by the monoamine brain levels, especially serotonin. In addition to its use in culture-bounded syndromes, the present findings of safety and efficacy give support to the proposal that T. alata may be used in the treatment of depression."

Journal • CNS Disorders • Depression • Mood Disorders • Psychiatry

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

Periosteal Osteosarcoma: Emerging Clinical Concepts, Evolving Treatment Options: A Narrative Review. (PubMed, Curr Pain Headache Rep) - "Adjuvant drugs can reduce inflammation and neuropathic pain, including corticosteroids, gabapentinoid agents such as gabapentin or pregabalin, lidocaine patches, tricyclic antidepressants such as amitriptyline, nortriptyline, and desipramine, or selective serotonin-norepinephrine reuptake inhibitors such as duloxetine and venlafaxine. The present investigation aims to synthesize currently available data on periosteal osteosarcomas, including common clinical, histologic, and radiographic presentations. In addition, this review aims to further examine the potential for biomarkers and provide recommendations for treatment and future research direction."

Journal • Review • Musculoskeletal Pain • Neuralgia • Oncology • Osteosarcoma • Pain • Sarcoma • Solid Tumor • TP53

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