maprotiline / Generic mfg. - LARVOL DELTA

Single-cell-level digital twins for preterm birth prevention strategies. (PubMed, bioRxiv) - "Tetrahydrofolate, maprotiline, and the combination of aspirin and lansoprazole emerged as top candidates for PTL prevention, delaying labor onset primarily through enhanced mTOR signaling in innate immune cells and attenuated JAK/STAT signaling in naïve CD4⁺ T cells. The codebase is available at https://github.com/ofondeur/SIMCO/ ."

Journal • CD4

Betanin, the primary phytochemical from the beet root plant, produces anxiolytic-like and diuretic-like effects in the chick social-separation stress test (Neuroscience 2025) - "Separate groups of chicks received either clonidine 0.15 mg/kg or maprotiline 2.5 mg/kg i.m 30 min prior to isolation for anxiolytic and antidepressant comparisons, respectively...These findings suggest betanin may be useful in the treatment of anxiety disorders but may possess diuretic effects. Future studies should attempt replicate betanin's anxiolytic-like effects and weight as well as measure betanin's effect on biomarkers associated with anxiety such as corticosterone and gut microbiota."

CNS Disorders • Depression • Mood Disorders • Psychiatry

O-GlcNAcylation of SPOP regulates colorectal cancer progression and ferroptosis by mediating β-catenin degradation. (PubMed, Cell Death Discov) - "Combined treatment with the SPOP-targeted drug maprotiline and a ferroptosis inducer has synergistic antitumor efficacy in CRC cells and xenografts. Our study reveals the multifaceted function of SPOP in CRC, and the activation of SPOP may be a feasible strategy to increase the sensitivity of CRC to ferroptosis inducers."

Journal • Colorectal Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • CTNNB1 • SLC7A11 • SPOP

The effects of antidepressants on cardiometabolic and other physiological parameters: a systematic review and network meta-analysis. (PubMed, Lancet) - "We found strong evidence that antidepressants differ markedly in their physiological effects, particularly for cardiometabolic parameters. Treatment guidelines should be updated to reflect differences in physiological risk, but choice of antidepressant should be made on an individual basis, considering clinical presentation and preferences of patients, carers, and clinicians."

Journal • Retrospective data • CNS Disorders • Mental Retardation • Metabolic Disorders • Psychiatry

Beyond mood: a systematic review and network meta-analysis of the physiological and cardiometabolic effects of antidepressants (ECNP 2025) - "Clinically meaningful differences included approximately 4 kg variation in weight change, with significant weight loss observed for agomelatine and marked weight gain for maprotiline. Cardiovascular effects varied notably; nortriptyline increased heart rate by over 21 bpm relative to fluvoxamine, which decreased it...While paroxetine, duloxetine, desvenlafaxine, and venlafaxine decreased body weight, they significantly raised total cholesterol levels, with duloxetine additionally elevating glucose. Liver enzyme elevations were consistently observed with duloxetine, desvenlafaxine, and levomilnacipran, though these were not deemed clinically significant...Healthcare organisations recommend that consideration and discussion of potential side effects should form an integral part of the antidepressant prescribing process (3). Incorporating these differential physiological risks into clinical guidelines can support tailored prescribing decisions, balancing psychiatric..."

Retrospective data • Review • Bipolar Disorder • CNS Disorders • Depression • General Anxiety Disorder • Major Depressive Disorder • Mental Retardation • Mood Disorders • Musculoskeletal Pain • Obsessive-Compulsive Disorder • Post-traumatic Stress Disorder • Psychiatry • Schizophrenia

THE PHYSIOLOGICAL AND CARDIOMETABOLIC EFFECTS OF ANTIDEPRESSANTS: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS (WPA-WCP 2025) - "Clinically meaningful differences included approximately 4kg variation in weight change, with significant weight loss observed for agomelatine and weight gain for maprotiline. Nortriptyline increased heart rate by over 21 bpm relative to fluvoxamine, which decreased it...While paroxetine, duloxetine, desvenlafaxine, and venlafaxine decreased body weight, they significantly raised total cholesterol levels, with duloxetine additionally elevating glucose...Conclusions Our findings highlight clinically relevant variations in adverse effects across antidepressants, particularly cardiometabolic parameters. Incorporating these physiological risks into practice can support tailored prescribing decisions, balancing psychiatric efficacy with patient-specific physical health considerations and preferences."

Retrospective data • Review • CNS Disorders • Mental Retardation • Psychiatry

Utilization of psychotropic drugs in Serbia from 2006 to 2021: Patterns before and during the COVID-19 pandemic. (PubMed, PLoS One) - "The COVID-19 pandemic did not contribute to change in consumption of psychotropic drugs in Serbia. Still, the use of antidepressants, atypical antipsychotics, anxiolytics, sedatives, hypnotics, anti-dementia drugs and gabapentinoids increased from 2006 to 2021."

Journal • Alzheimer's Disease • CNS Disorders • Dementia • Infectious Disease • Mental Retardation • Novel Coronavirus Disease • Psychiatry

Targeting the akt/mtor signaling pathway by maprotiline leads to tumor suppression in T-cell lymphoma. (PubMed, Ann Hematol) - "Notably, we discovered that maprotiline substantially enhances the sensitivity of TCL cells to histone deacetylase inhibitor, thereby unveiling a promising combination therapeutic strategy for TCL treatment. These findings not only expand our understanding of maprotiline's pharmacological potential beyond its conventional antidepressant use, but also provide a novel therapeutic avenue for addressing the clinical challenges in TCL management."

Journal • CNS Disorders • Depression • Hematological Malignancies • Lymphoma • Oncology • Psychiatry • T Cell Non-Hodgkin Lymphoma

Lessons Learned From Over Forty Years of Translational Neuroscience Research in Psychiatry: Implications for Drug Development: Nasrallah Family Award (APA 2025) - "Mifepristone, a progesterone and cortisol receptor antagonist, was then reported to be rapidly effective in reducing psychotic features, indicating elevated cortisol plays a role in pathogenesis and is not an epiphenomenon...In Phase III, response was seen primarily in patients who attained blood levels above a so-called therapeutic blood level, somewhat reminiscent of research with maprotiline...Here, there is a need for thinking "out of the box." For example, short forms of the serotonin transporter promoter are associated with poor response to SSRI's but our group has demonstrated this poor response actually reflects intolerance to the drugs' side effects. Instructional Level Introductory; Learning Objectives Objective One: Have a working knowledge of how translational neuroscience can influence new drug development Objective Two: Understand the basic organization and function on the hypothalamic pituitary adrenal (HPA) stress axis and issues learned..."

CNS Disorders • Depression • Epilepsy • Major Depressive Disorder • Psychiatry

Treatment with antidepressant drugs and hyponatremia: a network meta-analysis. (PubMed, J Endocrinol Invest) - "These data appear useful on clinical grounds, in order to increase the awareness regarding the possibility that antidepressants induce hyponatremia and to encourage regular serum sodium monitoring."

Journal • Retrospective data • Review • Cardiovascular • Heart Failure

An Exploration of the Interplay Between Caffeine and Antidepressants Through the Lens of Pharmacokinetics and Pharmacodynamics. (PubMed, Eur J Drug Metab Pharmacokinet) - "The interaction between fluvoxamine and caffeine resulted in increased concentrations of caffeine in the body and lowered the renal clearance of fluvoxamine. Other SSRIs such as fluoxetine and escitalopram had augmented antidepressant effects by decreasing their renal clearance and prolonging their effects in the body when coadministered with caffeine. Caffeine may also increase the concentration of paroxetine, potentially affecting its pharmacodynamic effects. TCAs such as clomipramine, imipramine, desipramine, and sertraline, were found to reduce the metabolism of caffeine...The inhibition of caffeine at high doses when used with MAOIs such as tranylcypromine and phenelzine was found to lead to a higher likelihood of experiencing hypertension. Coadministration of caffeine with venlafaxine (SNRIs) suggests minimal interactions between the two substances and the pharmacodynamic effects of venlafaxine were unlikely to be impacted by caffeine consumption. Miscellaneous..."

Journal • PK/PD data • Review • Cardiovascular • CNS Disorders • Hypertension • Psychiatry

A Pharmacovigilance Study on Psychotropic Agent-Induced Urinary Retention Using the Japanese Adverse Drug Event Report Database. (PubMed, Drugs Real World Outcomes) - "Many psychotropic drugs induce UR, which may be owing to their pharmacological effects. Appropriate monitoring is needed, especially in patients with other risk factors for UR."

Adverse events • Journal • Benign Prostatic Hyperplasia • CNS Disorders • Depression • Psychiatry

Network Medicine-Based Strategy Identifies Maprotiline as a Repurposable Drug by Inhibiting PD-L1 Expression via Targeting SPOP in Cancer. (PubMed, Adv Sci (Weinh)) - "By applying Mnet-DRI to PD-L1, maprotiline (MAP), an antidepressant drug is repurposed, as a potential PD-L1 modifier for colorectal and lung cancers. Experimental validation revealed that MAP reduced PD-L1 expression by targeting E3 ubiquitin ligase speckle-type zinc finger structural protein (SPOP), and the combination of MAP and anti-CTLA4 in vivo significantly enhanced the antitumor effect, providing a new alternative for the clinical treatment of colorectal and lung cancer."

IO biomarker • Journal • Colorectal Cancer • Lung Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • PD-L1 • SPOP

Standardized pharmaco-sleep-electroencephalography as a preclinical tool for antidepressant drug profiling (Neuroscience 2024) - "We evaluated the possibility to employ this method to assess the dose-dependency of antidepressants, with distinct mechanisms of action (MOA): fluoxetine and maprotiline (at 2 to 20mg/kg and 2.5 to 20 mg/kg, respectively). This state-specific analysis facilitated discovery of state-dependent drug-effects. This may ultimately lead to better cross-species translation of electrophysiological effects of pharmacological modulations."

Preclinical • CNS Disorders • Depression • Mood Disorders • Psychiatry

Decoding therapeutic signatures: the contribution of pharmaco-electroencephalography in profiling antidepressant compounds (ECNP 2024) - "Here, we examined pharmaco-EGG responses of 3 antidepressants (fluoxetine, duloxetine and maprotiline), with distinct mechanisms of action, in wild-type C57BL/6 mice. Overall, these findings support the establishment of pharmaco-EEG "signatures" that are not only specific to the antidepressant class but also reflective of distinct mechanisms of action. This study paves the way to a larger characterization of multiple antidepressants considering different types of metrics and exploring state-dependent and structure-dependent profiles."

CNS Disorders • Depression • Mood Disorders • Psychiatry

Adverse event profiles of drug-induced liver injury caused by antidepressant drugs: a disproportionality analysis. (PubMed, Ther Adv Drug Saf) - "Among the identified 42 antidepressants, nefazodone (n = 47, ROR = 7.79, IC = 2.91), fluvoxamine (n = 29, ROR = 4.69, IC = 2.20), and clomipramine (n = 24, ROR = 3.97, IC = 1.96) had the highest ROR for cholestatic injury; mianserin (n = 3, ROR = 21.46, IC = 3.99), nefazodone (n = 264, ROR = 18.67, IC = 3.84), and maprotiline (n = 15, ROR = 5.65, IC = 2.39) for hepatocellular injury; and nefazodone (n = 187, ROR = 12.71, IC = 0.48), clomipramine (n = 35, ROR = 2.07, IC = 0.26), and mirtazapine (n = 483, ROR = 1.96, IC = 0.94) for severe drug-related hepatic disorders...There are limited reports on the adverse reactions of relatively new antidepressant drugs, such as milnacipran, viloxazine, esketamine, and tianeptine, and those not approved by the Food and Drugs Administration, such as reboxetine and agomelatine...Duloxetine and clomipramine were associated with three DILI categories, except hepatic failure. The disproportionality analysis cannot conclude on a definite..."

Adverse events • Journal • CNS Disorders • Depression • Hepatology • Liver Failure • Mental Retardation • Psychiatry

Maprotiline Prompts an Antitumour Effect by Inhibiting PD-L1 Expression in Mice with Melanoma. (PubMed, Curr Mol Pharmacol) - "Our research findings suggest that maprotiline enhances the antitumour immune response in mouse melanoma by inhibiting PD-L1 expression. This study may discover a new PD-L1 inhibitor, providing a novel therapeutic option for the clinical treatment of tumours."

IO biomarker • Journal • Preclinical • CNS Disorders • Depression • Melanoma • Oncology • Psychiatry • Solid Tumor • CD4 • CD8

On-Chip Electromembrane Surrounded Solid Phase Microextraction for Determination of Tricyclic Antidepressants from Biological Fluids Using Poly(3,4-ethylenedioxythiophene)-Graphene Oxide Nanocomposite as a Fiber Coating. (PubMed, Biosensors (Basel)) - "In the present study, on-chip electromembrane surrounded solid phase microextraction (EM-SPME) was employed in the determination of tricyclic antidepressants (TCAs), including amitriptyline, nortriptyline, imipramine, desipramine, maprotiline, and sertraline, from various biological fluids. Moreover, this method provided suitable precision and fiber-to-fiber reproducibility, with RSDs ≤ 8.4%. The applicability of the proposed setup was eventually investigated for extraction of the drugs from human bone marrow aspirate, urine, plasma, and well water samples, in which satisfactory relative recoveries, from 93-105%, were obtained."

Journal

Potentiometric Determination of Maprotiline Hydrochloride in Pharmaceutical and Biological Matrices Using a Novel Modified Carbon Paste Electrode. (PubMed, Sensors (Basel)) - "No significant effect was observed in several interfering species tested. The proposed electrode was used for the precise determination of maprotiline in pure solutions, urine samples, and a real sample-the drug Ludiomil."

Journal

Maprotiline restores ER homeostasis and rescues neurodegeneration via Histamine Receptor H1 inhibition in retinal ganglion cells. (PubMed, Nat Commun) - "Finally, we determine that maprotiline restores ER homeostasis by inhibiting HRH1-mediated Ca release from ER. In this work we establish maprotiline as a candidate neuroprotectant and HRH1 as a potential therapeutic target for glaucoma."

Journal • CNS Disorders • Glaucoma • Ocular Inflammation • Ophthalmology • Optic Neuritis • Pain

Effects of the LC mobile phase in vacuum differential mobility spectrometry-mass spectrometry for the selective analysis of antidepressant drugs in human plasma. (PubMed, Anal Bioanal Chem) - "The effect of LC mobile phase composition and flow rate (2-50 µL/min) on mobility behavior in vacuum differential mobility spectrometry (vDMS) was investigated for electrosprayed isobaric antidepressant drugs (AD); amitriptyline, maprotiline, venlafaxine; and structurally related antidepressants nortriptyline, imipramine, and desipramine. The LC-vDMS-SIM/MS method was compared to a LC-MRM/MS method, and in both cases, inter-assay precisions were lower than 12.5 and accuracies were in the range 91.5-110%, but with a four times reduced analysis time (2 min) for the LC-vDMS-SIM/MS method. This work illustrates that with vDMS, the LC mobile phase composition can be used to tune the ion mobility separation and to improve assay selectivity without additional hardware."

Journal

A Study of Maprotiline in Combination With Tamoxifen and Temozolomide for Recurrent Glioblastoma (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: University of Rochester | N=30 ➔ 0 | Not yet recruiting ➔ Withdrawn

Combination therapy • Enrollment change • Trial withdrawal • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor

Optimization of therapy in patients with epilepsy and psychiatric comorbidities: key points. (PubMed, Curr Neuropharmacol) - "Some antiseizure medications (ASMs), namely valproic acid, carbamazepine and lamotrigine, have mood-stabilising effects and are routinely used for the treatment of bipolar disorder in patients who do not have epilepsy. Gabapentin and especially pregabalin exert anxiolytic effects. However, a number of ASMs, in particular levetiracetam, topiramate, and perampanel, may contribute to psychiatric disorders, including depression, aggressive behaviour and even psychosis...Although most of these can be safely used at therapeutic doses, bupropion, some tricyclic antidepressants, maprotiline, and clozapine may alter seizure threshold and facilitate epileptic seizures...Prevalence of non-adherence in PWE and psychiatric comorbidities is reported to reach values even higher than 70%. A careful evaluation of all these aspects contributes to optimize therapy with positive impact on seizure control, psychiatric wellbeing and quality of life."

Journal • Bipolar Disorder • CNS Disorders • Depression • Epilepsy • Mental Retardation • Mood Disorders • Psychiatry

A Fully Automated Online SPE-LC-MS/MS Method for the Determination of 10 Pharmaceuticals in Wastewater Samples. (PubMed, Toxics) - "The compounds included in the method were antineoplastics (cabazitaxel, docetaxel, doxorubicin, etoposide, irinotecan, methotrexate, paclitaxel, and topotecan), renin inhibitors (aliskiren), and antidepressants (maprotiline). Due to the shorter overall run time of 15 min, including sample preparation, and reduced sample volume (0.9 mL), this on-line SPE-LC-MS/MS method was extremely convenient and efficient in comparison to the classical off-line SPE method. The proposed method was also highly sensitive and can be used for ultratrace quantification of the studied pharmaceuticals in wastewaters, providing useful data for effective environmental monitoring."

Journal • Oncology

Maprotiline Ameliorates High Glucose-Induced Dysfunction in Renal Glomerular Endothelial Cells. (PubMed, Exp Clin Endocrinol Diabetes) - "In conclusion, maprotiline displayed a protective effect on HG-challenged HRGECs, which was mediated by the regulation of PKC-α. These findings provide further evidence for the potential use of maprotiline for the treatment of DN."

Journal • Diabetes • Diabetic Nephropathy • Hypoglycemia • Nephrology • Renal Disease • TJP1