amoxapine / Generic mfg. - LARVOL DELTA

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

In vitro non-coding RNA signature of chemoconvulsants (Neuroscience 2023) - " Rat primary cortical cultures were exposed to 11 chemoconvulsants (4-aminopyridine, amoxapine, bicuculline, chlorpromazine, donepezil, kainic acid, pentylenetetrazol, picrotoxin, pilocarpine HCl, SNC80, strychnine HCl) for 24 h. Exposed cells were lysed, and total RNA was extracted for poly-A enriched RNA sequencing. Chemoconvulsant-induced dysregulation of ncRNAs was compound specific. Particularly, we found upregulation of snoRNAs and lncRNAs, which were previously found to be regulated by experimental and human epilepsy. Our analysis highlighted miRNA sponging, a prevalent regulatory mechanism of lncRNAs, to be among one of the predicted functions of identified lncRNAs."

Preclinical • CNS Disorders • Epilepsy

Optimization of a multiplexed, cell-based assay of neuronal function (Neuroscience 2023) - "For example, Amoxapine reduced the burst duration and increased the network burst frequency, while also eliminating the intra-burst oscillations and thus decreasing the LFP power in the alpha band. These results support the continued development and use of in vitro neural assays for high throughput drug discovery and safety assessment."

CNS Disorders

An integrated approach for early in vitro seizure prediction utilising hiPSC neurons and human ion channel assays (Neuroscience 2023) - "The CNS active therapies (amoxapine, bupropion, chlorpromazine, clozapine, diphenhydramine, paroxetine, quetiapine) all caused characteristic changes to electrical activity in key parameters indicative of seizure such as network burst frequency and duration. These studies highlight the potential utility of an integrated in vitro approach for early seizure prediction to provide mechanistic information and to support optimal drug design in early development, saving time and resources. Furthermore, this model offers great opportunity for further development towards discovery of novel anti-epileptics."

Preclinical • CNS Disorders • Epilepsy

RETOXIFICATION OF GLUCURONIDATED BILE ACIDS BY BETA-GLUCURONIDASE ENZYMES FROM INTESTINAL MICROBIOTA: A NOVEL TARGET FOR THE TREATMENT OF BILE ACIDS-RELATED DISEASES OF THE GUT-LIVER AXIS (AASLD 2023) - "For inhibition assays, the enzymatic reaction was performed with a pool of human (5♂: 5♀) or murine (4♂:4♀) feces in the presence of 200µM amoxapine... This study illustrates for the first time, the role of intestinal microbial GUS enzymes in the reactivation of nontoxic BAs into toxic acids. The sex-, enzymatic- pharmacological- and diet-dependent modulation of this activity is also revealed. Overall, our results identify these enzymes as novel pharmacological targets for the treatment of BA-related diseases of the gut-liver axis."

Cholestasis • Gastrointestinal Disorder • Hepatology

An integrated approach for early in vitro seizure prediction utilising hiPSC neurons and human ion channel assays. (PubMed, Toxicol Sci) - "The CNS active therapies (amoxapine, bupropion, chlorpromazine, clozapine, diphenhydramine, paroxetine, quetiapine) all caused characteristic changes to electrical activity in key parameters indicative of seizure such as network burst frequency and duration. The GABA antagonist picrotoxin increased all parameters, but the antibiotics amoxicillin and enoxacin only showed minimal changes...Overall, pro-seizurogenic compounds showed a distinct fingerprint in the ion channel/MEA panel. These studies highlight the potential utility of an integrated in vitro approach for early seizure prediction to provide mechanistic information and to support optimal drug design in early development, saving time and resources."

Journal • Preclinical • CNS Disorders • Developmental Disorders • Epilepsy

Pharmacological treatment of psychotic depression: a systematic review and network meta-analysis (ECNP 2023) - "Olanzapine plus fluoxetine demonstrated to be superior to olanzapine monotherapy (RR=1.60, 95% CI:1.09-2.34) and placebo (RR=1.91, 95% CI:1.27-2.85); amoxapine and the combination of perphenazine and amitriptyline were more efficacious then perphenazine alone (RR=3.14, 95% CI:1.01-9.80; RR=3.61, 95% CI:1.23-10.56)...A second subnetwork included four RCTs with a comprehensive sample of 188 participants (3.72% BD) on four antidepressants (fluvoxamine, imipramine, mirtazapine, and venlafaxine)...Testing the comparative efficacy of alternative antidepressant-antipsychotic combinations would be important, as the current evidence is limited to combinations including olanzapine or perphenazine. Other pharmacological (e.g., lithium) and non-pharmacological options (e.g., electroconvulsive therapy) should also be examined in future studies."

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

GABA receptor-mediated seizure liabilities: a mixed-methods screening approach. (PubMed, Cell Biol Toxicol) - "Amoxapine was one of the hits identified and subjected to an array of in vitro assays to examine molecular and cellular effects on neuronal excitability and in vivo locomotor pattern changes in zebrafish larvae...Inspired by the Adverse Outcome Pathway framework, we postulate several candidate pathways leading from specific binding sites to acute seizure induction. The whole workflow can be utilized for any compound collection and should inform about GABA receptor-mediated seizure risks more comprehensively compared to standard displacement screens, as it rests chiefly on functional data."

Journal • CNS Disorders • Epilepsy

An Evaluation of Tertiary Drug Resources' Consistency Regarding Drug-Drug Interactions Between Tricyclic Antidepressants and Herbal Supplements. (PubMed, J Pharm Technol) - " The following medications and herbal supplements were evaluated on Lexicomp, Micromedex, and Medscape: amitriptyline, nortriptyline, doxepin, imipramine, desipramine, amoxapine, St...John's Wort due to the risk of serotonin syndrome, several other discrepancies were noted, with regard to both the severity of the interaction indicated and whether or not an interaction was identified. It is imperative that clinicians be aware of potential discrepancies between tertiary drug information resources, including the potential for variation in both the clinical interpretation of its severity and the recognition of an interaction."

Journal

Amoxapine-Loaded Solid Lipid Nanoparticles with Superior Preclinical Pharmacokinetics for Better Brain Delivery: LC-MS/MS and GC-MS Analysis. (PubMed, ACS Chem Neurosci) - "Based on the findings, it appears that utilizing a solid lipid nanoparticle carrier to transport AMX can be a highly effective delivery method with improved pharmacokinetic properties in the brain. This approach may prove valuable for future antidepressant treatment."

Journal • PK/PD data • Preclinical • CNS Disorders • Depression • Psychiatry

Preparation and characterization of amoxapine- and naringin-loaded solid lipid nanoparticles: drug-release and molecular-docking studies. (PubMed, Nanomedicine (Lond)) - "NG showed a higher predicted binding affinity for CYP3A4 and CYP2D6, suggesting the potential for inhibition. The developed formulations were thoroughly characterized along with molecular docking data indicating promising AMX and NG combinations that may show good therapeutic activity."

Journal • CYP3A4

Successful Treatment of Amoxapine-Induced Intractable Seizures With Intravenous Lipid Emulsion. (PubMed, J Emerg Med) - "Although she was initially treated with intravenous diazepam, her seizures persisted. Levetiracetam and phenobarbital were then administered, but seizures persisted...Emergency physicians may consider ILE as an adjunctive therapy for amoxapine poisoning with a high mortality rate. ILE should be implemented carefully with monitoring of total dosage and adverse events."

Journal • CNS Disorders • Depression • Epilepsy • Psychiatry

FDA-Approved Amoxapine Effectively Promotes Macrophage Control of Mycobacteria by Inducing Autophagy. (PubMed, Microbiol Spectr) - "Using a cell-based screen of FDA-approved host-directed therapies (HDTs), we showed that Amoxapine inhibits macrophage cytotoxicity during mycobacterial infection and enhances the intracellular killing of mycobacteria within macrophages by activating the autophagy pathway, both in vitro and in vivo. These findings confirm targeted autophagy as an effective strategy for developing new HDT against mycobacteria."

FDA event • Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • ATG16L1