amoxapine / Generic mfg. - LARVOL DELTA

Infectious, inflammatory, and clinical outcomes among patients prescribed trifluoperazine or amoxapine: a retrospective cohort study using real-world data. (PubMed, Front Med (Lausanne)) - "Patients prescribed TFP, AXPN, fluoxetine, or no antidepressants/antipsychotics (general control) were assigned to mutually exclusive cohorts. These exploratory findings identify potential signals linking TFP and AXPN to infection susceptibility. Given the study design, these observations are hypothesis-generating and require confirmation in future prospective studies."

Clinical data • Journal • Real-world evidence • Retrospective data • CNS Disorders • Critical care • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • Septic Shock • CRP

Implementation of the In Vitro Seizure Liability Assay (iLAseizure) in Drug Discovery and Development: Mechanism of Action Case Studies. (PubMed, Pharmacol Res Perspect) - "Amoxapine (shows clinical seizures) gave concentration-dependent changes in MEA parameters and inhibited seizure-related ion channels with high potency (IC50 < 30 μM) at the human therapeutic concentration range (0.57-1.91 μM)...This work should be considered within the context of recent proposed updates to safety pharmacology guidelines, such as ICH S7A. However, further work is needed to validate assay performance and clarify the context of use."

Journal • Preclinical • CNS Disorders • Developmental Disorders • Epilepsy

Building structure activity relationships (SAR) to avoid toxicity due to unwanted CNS ion channel activity. (PubMed, Toxicol Sci) - "SAR test compounds were selected from the Enamine REadily AccesibLe (REAL) database using pharmacophore features and similarity to previous test compounds (amoxapine, diphenhydramine, quetiapine, 4-AP, linopirdine) or to ion channel positive reference compounds (bepridil, NS1619, quinidine, verapamil, XE991). The seizure-like phenotype was altered with the derivatives, as expected from the respective ion channel IC50 values. These data provide insight into specific substructures associated with seizure-like drug toxicity, offering the opportunity to avoid CNS liability in the development of novel compounds, saving time, money and resources."

Journal • CNS Disorders • Developmental Disorders • Epilepsy • NAV1

Association of Antidepressant Class With Suicide Risk in Adults (APA 2026) - "Exposures: Initiation of SSRI monotherapy (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, or vilazodone) versus TCA monotherapy (trimipramine, clomipramine, desipramine, doxepin, imipramine, amitriptyline, amoxapine, or nortriptyline). Among matched patients (mean age 47.8 years; 67% female), SSRI initiation was associated with higher 30-day suicide-related risk compared with TCAs (HR, 1.59; 95% CI, 1.39–1.80), with elevation persisting to 1 year (HR, 1.27; 95% CI, 1.20–1.35) and attenuating thereafter. Young adults had the greatest early risk (18–24 years: 30-day HR, 3.72; 95% CI, 2.03–6.81). Findings were consistent across sex and racial groups and robust to sensitivity analyses."

Clinical • Alzheimer's Disease • CNS Disorders • Dementia • Depression • Major Depressive Disorder • Mood Disorders

A case of pregnancy following surgery for imperforate anus with absent prostate and seminal vesicles. (PubMed, Int J Surg Case Rep) - "Despite drug therapy with amoxapine, there was no improvement, and he underwent intravesical sperm retrieval...We have experienced a case of successful pregnancy following imperforate anus surgery with congenital absence of the prostate and seminal vesicles. With appropriate treatment, patients with ejaculatory disorder after imperforate anus surgery can still impregnate a partner."

Journal • Infertility • Sexual Disorders

Cytochrome P450 2D6 (CYP2D6) Inhibition by Bergamottin and Diosmetin as a Strategy to Enhance the Pharmacokinetics and Antidepressant Efficacy of Amoxapine. (PubMed, ACS Pharmacol Transl Sci) - "In vitro CYP2D6 inhibition assays demonstrated that BER and DIO significantly suppressed CYP2D6-mediated dextromethorphan metabolism in a concentration-dependent manner, while rat liver microsome studies showed markedly improved metabolic stability of AMX, with reduced intrinsic clearance and extended half-life in the presence of BER and DIO compared with AMX alone. These findings demonstrate that BER and DIO augment the pharmacokinetic and pharmacodynamic profiles of AMX through CYP2D6 inhibition and improved brain delivery, supporting their potential as natural bioenhancers to enhance antidepressant efficacy. This combination strategy represents a promising approach for developing superior AMX-based therapeutic regimens and warrants further clinical investigation."

Journal • PK/PD data • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • CYP3A4

Evaluation of toxicokinetic interactions mediated by plasma protein binding during amoxapine intoxication. (PubMed, J Toxicol Sci) - "Toxicity enhancement mediated by plasma protein binding during intoxication remains poorly understood. In addition, chlorpromazine inhibits AMX binding to α1-acid glycoprotein; however, AMX may alternatively binds to albumin, which results in no apparent change in the total binding ratio. Further insights into the toxicokinetic interactions mediated by plasma protein binding are also needed for various toxic substances other than AMX."

Journal

Building structure activity relationships (SAR) to avoid unwanted CNS ion channel activity (Neuroscience 2025) - "Compounds were selected from the Enamine REAL database with machine learning approaches using pharmacophore features and similarity to the selected test compounds from the original screen (amoxapine, diphenhydramine, quetiapine, 4-AP, linopirdine, bepridil, NS1619, quinidine, verapamil, XE991). Future work testing the compound set across more ion channels will provide more evidence and help to build a SAR predictive tool. This will help medicinal chemists avoid liability in the development of novel compounds."

CNS Disorders • Epilepsy • CAV2 • NAV1

Neurological risk and protective associations of amoxapine and trifluoperazine: Retrospective cohort analysis from real-world data (Neuroscience 2025) - "Grant Support Clinical and Translational Science Award (UL1 TR001439) from the National Center for Advancing Translational Sciences, National Institutes of Health Trifluoperazine (TFP) and amoxapine (AXPN) are FDA-approved psychotropic medications with established central nervous system activity. Overall findings suggest a significantly lowered risk of mild cognitive impairment and restless leg syndrome for TFP compared to fluoxetine, while AXPN and fluoxetine showed no significant differences. The findings suggest potential neurological effects of TFP and support the need for further investigation into its repurposing potential for neuroprotection."

Real-world • Real-world evidence • Retrospective data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Epilepsy • Mental Retardation • Movement Disorders • Parkinson's Disease • Psychiatry • Restless Legs Syndrome • Sleep Disorder

Assessment of Erroneous Allergy Documentation of Amoxapine with Look Alike Sound Alike Drugs. (PubMed, Hosp Pharm) - No abstract available

Journal • Allergy • Immunology

Setup and Evaluation of the TRACT Assay Principle for the In Vitro Functional Characterization of Modulators of the Serotonin Transporter and the Serotonin 2A Receptor. (PubMed, Anal Chem) - "Obtained inhibition potencies ranged from 2.61 nM for paroxetine to 348 nM for naphyrone, and good agreement in rank order was obtained when compared with the outcome of a fluorescence-based and a radioactivity-based uptake assay...Additionally, for amitriptyline and amoxapine, the TRACT assay indicated direct (non-SERT mediated) 5-HT2AR-modulating effects, caused by inverse agonism, as confirmed by the 5-HT2AR βarr2 recruitment assay. We also demonstrate a proof-of-principle for applying this system to detect SERT-mediated efflux. Overall, our findings support the utility of the TRACT assay for the characterization of SERT ligands."

Journal • Preclinical • Psychiatry • ARRB1

Successful Treatment of Anemia With Ringed Sideroblasts Induced by Antidepressants Through Vitamin B6 Supplementation and Discontinuation of Antidepressants. (PubMed, Case Rep Hematol) - "His anemia improved significantly with VB6 supplementation and resolved completely after discontinuing amoxapine. This case highlights the need to consider VB6 deficiency in anemia with ringed sideroblasts."

Journal • Anemia • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

In vitro seizure risk assessment using a microelectrode array and comparison with an in vivo rat study. (PubMed, Toxicol Sci) - "Here we investigated the usefulness of in vitro microelectrode array (MEA) assays using rat primary neurons by comparing them with an in vivo convulsion study for fourteen reference drugs known to cause seizure/convulsion: paroxetine, 4-aminopyridine, pentylenetetrazol, strychnine, amoxapine, fluvoxamine, linopirdine, theophylline, pilocarpine, tramadol, bupropion, diphenhydramine, kainic acid, and veratridine. The NBF threshold for seizure could be used to predict the CSF concentrations of some drugs in rats with convulsions. Thus, an in vitro MEA assay using rat primary neurons can predict the risk of in vivo convulsions, which could be useful for drug screening during the early stage of drug candidate selection."

Journal • Preclinical • CNS Disorders • Epilepsy

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

Optimized ebselen derivatives as novel potent Escherichia coli β-glucuronidase covalent allosteric inhibitors. (PubMed, Eur J Med Chem) - "Among these, twenty-five BSEA derivatives demonstrated greater inhibitory efficacy than the most potent known EcGUS inhibitor, amoxapine (AMX), with compound 49 showing the strongest activity, achieving an IC50 of 12.9 nM. Molecular docking predicted specific interactions, such as hydrogen bonds involving Se and the pyrazole NH of compound 49 with Cys28 and Cys449, which may contribute to its inhibitory action. This study reports the first discovery of covalent inhibitors for EcGUS, with optimized BSEA derivatives acting as novel allosteric covalent inhibitors, revealing structure-activity relationships and molecular determinants that establish their potential in drug development."

Journal

MULTI-BIOINFORMATICS REVEALED DRUGGABLE PROTEIN NETWORK OF PROGRESSION FROM GASTRIC INTESTINAL METAPLASIA TO GASTRIC ADENOCARCINOMA (UEGW 2024) - "Computational drug repurposing of approved and investigational drugs/compounds (e.g., as found on www.clinicaltrials.gov) identified the following drugs as effective for GIM: dasatinib with or without erlotinib, nilotinib, afatinib on SRC, SM1-71 on SRC, JNJ-26483327 on EGFR, Afatinib on EGFR, ingenol mebutate on protein kinase C (PKC) family, amoxapine, benoxaprofen, avobenzone, amlexanox, alprazolam, praziquantel, ibuprofen piconol, tranilast, and restoril. The druggable protein network associated with GIM progression toward GA was identified. The distinct phenotypic patterns between GIM and GA might challenge the notion that GIM serves as the primary precancerous lesion in GA tumorigenesis rather than shares a common cause with tissue-resident stem cells. Further validation of the druggable protein network is needed for the development of a cost-effective surveillance program and preventive treatment of the GIM-to-GA progression."

IO biomarker • Breast Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRCA1 • CD44 • CTNNB1 • EGFR • JUN • RBP2 • SRC

Drug Repositioning Analysis Identified Hundreds of Novel Compounds Associated With Tobacco Use Disorder (WCPG 2024) - "The medications that significantly reversed (Bonferroni p<6.03E-05) the transcriptional profile associated with TUD included varenicline (a well-known therapeutic for smoking cessation), sodium channel blockers (e.g., amiloride), and compounds that are used to treat conditions that commonly co-occur with TUD, such as antipsychotics (e.g., clozapine), dopaminergic agents (e.g., ropinirole), opioids (e.g., nalbuphine), and antidepressants (e.g., amoxapine), among others. Approaches such as this one open new avenues for identifying already FDA-approved compounds that might be effective treatments for TUD."

Addiction (Opioid and Alcohol) • CNS Disorders • Nicotine Addiction • Tobacco Addiction • Tobacco Cessation • DRD2

Clinical case of 45,X/46,XY mosaic male with ejaculatory disorder associated with seminal vesicle dysplasia: a case report. (PubMed, Sex Med) - "Treatment strategies included attempted varicocelectomy, pharmacological intervention with amoxapine, and surgical testicular sperm extraction...Consequently, surgical retrieval of testicular sperm was performed, leading to successful pregnancy via ICSI for his wife. Our approach has effectively addressed ejaculatory disorder in 45,X/46,XY mosaic men, resulting in successful pregnancy."

Journal • Infertility • Sexual Disorders • Turners Syndrome

Exploring the correlation between cardiovascular adverse events and antidepressant use: A retrospective pharmacovigilance analysis based on the FDA Adverse Event Reporting System database. (PubMed, J Affect Disord) - "The retrospective analysis revealed that cardiovascular AEs were connected with antidepressant use, and the binding/uptake inhibitory potency and selectivity of neurotransmitters of antidepressants played an important role, providing a preliminary basis for further in-depth study of antidepressant-related cardiovascular toxicity. However, as an exploratory study, prospective studies are needed to validate our findings in the future."

Adverse events • Journal • Retrospective data • Atrial Fibrillation • Cardiomyopathy • Cardiovascular • CNS Disorders • Coronary Artery Disease • Depression • Heart Failure • Hypertension • Psychiatry • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Depolymerization of Waste Polycarbonates to Value Added Products. (PubMed, ChemSusChem) - "The developed method deals with depolymerization of waste polycarbonates and works even with late-stage amine derivatives such as amoxapine and desloratadine which are drugs molecules known to treat neurotic disorders and allergies respectively. The reaction can be scaled up and works with similar efficacy which depicts the efficiency of the depolymerization of end-of-life polycarbonate plastic waste. The biscarbamate and bisphenol-A was further subjected for the post functionalization to obtain amides and phenol in good yields."

Journal • Allergy • Immunology

Gut microbiota biotransformation of drug glucuronides leading to gastrointestinal toxicity: Therapeutic potential of bacterial β-glucuronidase inhibition in mycophenolate-induced enteropathy. (PubMed, Life Sci) - "Collectively, these results suggest that the digestive accumulation of MPA is involved in the pathophysiology of MPA-gastrointestinal adverse effects. This study provides a proof-of-concept of the therapeutic potential of bacterial β-G inhibitors in glucuronidated drug-induced enteropathy."

Journal • Gastrointestinal Disorder

Pharmacological treatments for psychotic depression: a systematic review and network meta-analysis. (PubMed, Lancet Psychiatry) - "According to the available evidence, the combination of a selective serotonin reuptake inhibitor and a second-generation antipsychotic-and particularly of fluoxetine and olanzapine-could be the optimal treatment choice for psychotic depression. These findings should be taken into account in the development of clinical practice guidelines. However, these conclusions should be interpreted cautiously in view of the low number of included studies and the limitations of these studies."

Journal • Retrospective data • Review • Bipolar Disorder • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Inhibitory Actions of Antidepressants, Hypnotics, and Anxiolytics on Recombinant Human Acetylcholinesterase Activity. (PubMed, Biol Pharm Bull) - "At a concentration of 10 M, 22 antidepressants, 19 hypnotics, and 11 anxiolytics inhibited rhAChE activity by <20%, whereas nine antidepressants (clomipramine, amoxapine, setiptiline, nefazodone, paroxetine, sertraline, citalopram, escitalopram, and mirtazapine), two hypnotics (triazolam and brotizolam), and one anxiolytic (buspirone) inhibited rhAChE activity by ≥20%. Among these drugs, only nefazodone inhibited rhAChE activity within the blood concentration range achievable at clinical doses. Therefore, nefazodone may not only improve the depressive symptoms of BPSD through its antidepressant actions but also slow the progression of cognitive symptoms of AD through its AChE inhibitory actions."

Journal • Alzheimer's Disease • CNS Disorders • Dementia • Pain

Drugs for depressionr. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • CNS Disorders • Depression • Mood Disorders • Psychiatry

Serotonin syndrome: A pharmacovigilance comparative study of drugs affecting serotonin levels. (PubMed, Eur J Clin Pharmacol) - "Prescribers need to be vigilant about drugs that can raise serotonin concentration or influence serotonergic neurotransmission, also when using drugs with less well-known risk for serotonin syndrome, like linezolid and triptans."

Adverse events • Journal