tranylcypromine / Generic mfg. - LARVOL DELTA

Cytochrome P450-Catalyzed Hydroxylation of Δ8-Tetrahydrocannabinol and Implications for Pharmacogenetics. (PubMed, Pharmaceutics) - "Inhibition of 11-OH-Δ8-THC formation in rCYP-overexpressing microsomes was observed when using CYP probe inhibitors (sulfaphenazole for CYP2C9 and tranylcypromine for CYP2C19)... Given that the expression of CYP2C9 is much higher than that of CYP2C19 in both human intestine and liver, these data suggest that CYP2C9 is the primary enzyme responsible for intestinal 11'-hydroxylation of Δ8-THC and that other untested CYPs may be important in hepatic Δ8-THC hydroxylation. In addition, the reduced 11-OH-Δ8-THC formation activity observed with CYP2C9 variants (*2, *3, *8, *9) suggests interindividual variability in Δ8-THC disposition."

Biomarker • Journal • CYP2C19 • CYP2C9

Sensitization of Non-M3 Acute Myeloid Leukemia Blasts to All-Trans Retinoic Acid by the LSD1 Inhibitor Tranylcypromine: TRANSATRA Phase I Study. (PubMed, Eur J Haematol) - "As histone demethylase LSD1 (KDM1A) is a rational therapeutic target in AML, we conducted a phase I trial ("rolling-six design") with the LSD1 inhibitor tranylcypromine (TCP, dose levels [DL] 20, 40, 60, 80 mg p.o. d1-28) combined with fixed-dose ATRA (45 mg/m2 p.o. d10-28) and low-dose cytarabine (LDAC, 40 mg s.c. Trial Registration: German Clinical Trials Register (DRKS): DRKS00006055. For further Information see https://drks.de/search/en/trial/DRKS00006055."

Journal • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

The dual roles of lysine-specific demethylase 1 (KDM1A/LSD1) in the modulation of tumor immune microenvironment and its inhibitors in colorectal cancer. (PubMed, J Mol Med (Berl)) - "Clinically, small-molecule inhibitors targeting KDM1A, such as Tranylcypromine (TCP) and Iadademstat, could enhance the efficacy of ICIs by reversing the immunosuppressive microenvironment, especially in mismatch repair proficient (pMMR) CRC. Future studies should further elucidate the molecular networks of KDM1A regulating immunogenicity and explore the synergistic mechanisms of its inhibitors with other epigenetic drugs or immunotherapies in order to provide new strategies for overcoming CRC resistance to immunotherapies."

Journal • Review • Colorectal Cancer • Oncology • Solid Tumor • CTNNB1

Integrated Bioinformatic and Experimental Analysis Reveals the Molecular Mechanisms Underlying KDM1B/LSD2 Inhibition as a Therapeutic Strategy in Human Lung Adenocarcinoma. (PubMed, J Cell Biochem) - "Moreover, cell proliferation was significantly inhibited by the KDM1B inhibitor, tranylcypromine, and induced G0/G1 phase cell cycle arrest, increased apoptosis, ROS, and glycolytic activity in A549 cells. Collectively, these findings highlight KDM1B as a valuable therapeutic target in lung adenocarcinoma and emphasize its key role in lung cancer development."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

LSD1-based dual-target inhibitors as emerging anticancer agents: pharmacological perspectives and SAR exploration. (PubMed, Future Med Chem) - "This review aims to provide recent design strategies and SAR for LSD1-based dual inhibitors, emphasizing the fusion of different LSD1 pharmacophore (tranylcypromine, pargyline, pyridine, 5-cyano-3-phenylindole, indole, benzyl/aryl piperazine, triazole-dithiocarbamate and substituted triazole scaffold) with various heterocyclic and zinc-binding cores such as hydroxamic acids, bipyridine, hydroxy quinoline to generate hybrids capable of inducing apoptosis, blocking cell-cycle, differentiation. This review explores the pharmacological role of LSD1 in oncogenesis and offers structural and SAR insights to guide the design of LSD1-based dual inhibitors."

Journal • Review • Acute Myelogenous Leukemia • Colorectal Cancer • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • EGFR

Cytochrome P450-catalyzed hydroxylation of Δ8-tetrahydrocannabinol and implications for pharmacogenetics. (PubMed, Res Sq) - "Inhibition of 11-OH-Δ8-THC formation in rCYP overexpressing microsomes was observed when using CYP probe inhibitors (sulfaphenazole for CYP2C9 and tranylcypromine for CYP2C19)...Given that the expression of CYP2C9 is much higher that CYP2C19 in both human intestine and liver, these data suggest that CYP2C9 is the primary enzyme responsible for intestinal 11'-hydroxylation of Δ8-THC and that other untested CYPs may be important in hepatic Δ8-THC hydroxylation. In addition, the reduced 11-OH-Δ8-THC formation activity observed with CYP2C9 variants (*2, *3, *8, *9) suggests interindividual variability in Δ8-THC disposition."

Biomarker • Journal • CYP2C19 • CYP2C9

Stereospecific Epoxide-to-Cyclopropylamine Conversion by a Homologous Horner-Wadsworth-Emmons-Type Reaction With an Imine-Substituted Phosphine Oxide. (PubMed, Angew Chem Int Ed Engl) - "The strategy's robustness is demonstrated by the efficient, scalable synthesis of the core scaffolds of bioactive molecules such as ticagrelor and tranylcypromine. DFT calculations elucidate the role of the imino group in facilitating the reaction and illustrate the origin of diastereoselectivity through a rigid, chelated transition state model."

Journal

Insomnia, Sleep, and the Use of Sedative-Hypnotic Drugs: Practical Notes. (PubMed, J Clin Psychiatry) - "Issues examined include the choice of drug for sleep-onset insomnia and for sleep-maintenance insomnia; the choice of drug for insomnia in patients with psychiatric disorders; sedative-hypnotic dosing in contexts such as perturbation of multiple neurotransmitter systems; metabolic drug interactions with sedative-hypnotic drugs; gastrointestinal absorption of hypnotic drugs and time to onset of drowsiness; the effect of food on absorption and time to onset of drowsiness; the effect of glucagon-like peptide-1 receptor agonist (GLP-1RA) drugs on absorption and time to onset of drowsiness; the importance of half-life for the duration of action of the sedative-hypnotic drug; strategies to address oversedation with sedating psychotropic drugs; treating insomnia with classical monoamine oxidase inhibitors, especially tranylcypromine; optimization of sedative-hypnotic therapy; provision of patient guidance; and related matters. Readers are also reminded that sleep hygiene and..."

Journal • Anesthesia • CNS Disorders • Insomnia • Mental Retardation • Psychiatry • Sleep Disorder

Muse-like stem cell therapy for curing chronic diseases in geriatric feline and canine. (PubMed, Front Vet Sci) - "Screening of over 100 small-molecule compounds identified optimized five-compound cocktails-valproic acid (0.5 mM), CHIR99021 (3 μM), PD0325901 (0.5 μM), Trolox (10 μM), and nicotinamide (1 mM) for feline MSCs; parnate (10 μM), CHIR99021 (3 μM), PD0325901 (0.5 μM), Trolox (10 μM), and Y27632 (10 μM) for canine MSCs. A small molecule cocktail method was introduced to enhance the Muse population in MSCs, which provide a safe and effective way to harvest Muse cells. These Muse-like MSCs demonstrate high clinical potential for chronic and age-related degenerative diseases, making it a safe and effective therapeutic option."

Journal • Hepatology • Inflammation • Nephrology • Renal Disease • KRT7 • NES

Design and optimization of selective and potent LSD1 inhibitors with tranylcypromine-pyrimidine scaffold for the treatment of acute myeloid leukemia. (PubMed, Bioorg Chem) - "7a induced apoptosis while upregulating the differentiation marker CD86 and downregulating the stem cell-associated proteins SOX2 and CD44. Collectively, these findings establish compound 7a, a tranylcypromine-pyrimidine derivative, provides the structural foundation for the development of LSD1 inhibitors for the treatment of AML."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD86 • SOX2

Tranylcypromine: a promising repurposed drug against Leishmaniases. (PubMed, Front Microbiol) - "Viability and cytotoxicity assays on THP-1-derived macrophages highlighted that the compound, at the selected concentrations, was safe and did not induce a toxic effect on host cells with CC50 values exceeding 280 μg/ml. Altogether, these findings revealed Tranylcypromine as a selective and promising antileishmanial drug candidate, supporting the relevance of AI-assisted drug repurposing strategies to accelerate drug discovery of safe and affordable therapies for neglected tropical diseases."

Journal

Inhibition of CYP2A6-mediated nicotine metabolism: A potential strategy for smoking cessation therapy. (PubMed, J Pharmacol Exp Ther) - "In this review, we discuss 4 CYP2A6 inhibitors, methoxsalen, tranylcypromine, 5-(4-ethylpyridin-3-yl)thiophen-2-yl)methanamine, and cannabidiol, describing their potency, translational potential, and safety considerations...With additional research, CYP2A6 inhibition could become a practical and personalized way to improve smoking cessation outcomes. SIGNIFICANCE STATEMENT: This study highlights the clinical significance of inhibiting CYP2A6-mediated nicotine metabolism as a novel smoking cessation strategy by reviewing in vitro, preclinical, and clinical data of agents that mimic the slow CYP2A6 metabolizer phenotype and improve smoking cessation outcomes."

Journal • Review • Tobacco Cessation • CYP2A6

Drug-associated hypertensive crisis: a disproportionality analysis of the FAERS database. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Ramipril (282 cases) and valsartan (192 cases) ranked as the second and third medications, respectively. The top 5 drugs associated with the risk of hypertensive crisis under the ROR algorithm were amlodipine perindopril (ROR = 136.64), methyl aminolevulinate (ROR = 122.78), tranylcypromine (ROR = 105.15), rifapentine (ROR = 39.46), and amiloride hydrochlorothiazide (ROR = 39.36)...Our study showed that numerous medications carry potential risks for drug-associated hypertensive crisis. Further investigation is required to establish causality and inform clinical decision-making."

Journal

NLRP3 inflammasome and hearing loss: from mechanisms to therapies. (PubMed, J Neuroinflammation) - "Experimental studies have demonstrated that pharmacological inhibition of NLRP3 via agents such as MCC950, oridonin and tranylcypromine can preserve auditory function...Clinically, IL-1B signaling blockers such as anakinra and canakinumab have shown efficacy in CAPS patients, stabilizing or improving hearing outcomes...Future translational research should focus on validating NLRP3-targeting compounds in human trials, identifying biomarkers for early diagnosis, and exploring combination therapies that integrate anti-inflammatory, antioxidant, and regenerative strategies. Targeting NLRP3 may ultimately redefine treatment paradigms for preventing or halting progressive hearing loss."

Journal • Review • Inflammation • Otorhinolaryngology • Rare Diseases • IL18 • IL1B • NLRP3

Tranylcypromine-derived LSD1 inhibitors: Synthetic strategies, structure-activity relationships, and anticancer potential. (PubMed, Eur J Med Chem) - "Clinically evaluated candidates like TCP, ORY-1001, and INCB059872; administered alone or in combination; irreversibly inhibit LSD1 by binding its FAD cofactor. Collectively, these inhibitors demonstrate significant therapeutic promise. We further discuss challenges (e.g., selectivity, resistance), opportunities, and future directions for optimizing LSD1-targeted cancer therapies."

Journal • Review • Breast Cancer • Oncology • Solid Tumor

Quercetin and Tranylcypromine Improve Memory, Behavioral Performance, and Cholinergic Function in Male Rats Subjected to Chronic Restraint Stress. (PubMed, Brain Sci) - "Overall, quercetin and TCP proved to reverse CRS-induced alterations in these parameters. Quercetin mitigated cognitive deficits, behavioral impairments, and neurochemical alterations induced by the CRS model, especially in association with TCP, supporting its potential as a promising therapeutic agent for depression."

Journal • Preclinical • CNS Disorders • Cognitive Disorders • Depression • Major Depressive Disorder • Mood Disorders • Pain • Psychiatry

MAO inhibitors for treatment-resistant depression: bringing an updated perspective on pioneering drugs. (PubMed, Pharmacol Res) - "These now have well-recognized mechanisms of action, making them much less common and potentially preventable. It is important to study and teach the pharmacology of monoamine oxidase inhibitors again in order to revive their use in severely depressed patients, as well as in those who have experienced multiple treatment failures."

Journal • Review • CNS Disorders • Depression • Mental Retardation • Mood Disorders • Psychiatry

Tangeretin protects the kidney from ischemia-reperfusion injury by inhibiting inflammatory response through downregulation of MAOA. (PubMed, Int Immunopharmacol) - "Tangeretin attenuates RIRI-induced renal injury by inhibiting the MAOA/NF-κB pathway and exerting anti-inflammatory and anti-apoptotic effects. These findings highlight its potential as a promising therapeutic candidate for ischemia-associated AKI."

Journal • Acute Kidney Injury • Cardiovascular • Inflammation • Nephrology • Renal Disease • Reperfusion Injury

Rapid Monoamine Oxidase Inhibitor Switches in Treatment-Resistant Depression: Safety Evaluation in 3 Cases. (PubMed, J Psychiatr Pract) - "Case 1: A 25-year-old female on selegiline for 2 months was switched to phenelzine with only 1 medication-free day, then switched to tranylcypromine 2 weeks later with 1 medication-free day...Case 3: A 41-year-old female on isocarboxazid was switched to phenelzine with a 1-day washout period. The switch was well tolerated without any adverse events. These findings suggest MAOIs can be safely switched with a washout period of 2 days or less, although this should be reserved for specific clinical situations where the expected benefits outweigh the potential risks associated with any direct antidepressant switch."

Journal • CNS Disorders • Depression • Mood Disorders • Psychiatry

Unravelling the target landscape of tranylcypromines for new drug discovery. (PubMed, Acta Pharm Sin B) - "Tranylcypromine (TCP) is a widely acknowledged scaffold with diverse pharmacological activities...Notably, the first reversible oral P2Y12 receptor antagonist, ticagrelor, is currently used to prevent future myocardial infarction, stroke, and cardiovascular death...This review aims to explore the target landscape of TCPs, highlight key structure-activity relationships (SARs), and emphasize the therapeutic potential of TCPs for treating various diseases. Finally, the lessons learned from our medicinal chemistry practice, challenges and future directions of TCP-based drug discovery are briefly discussed."

Journal • Review • Acute Coronary Syndrome • Cardiovascular • Human Immunodeficiency Virus • Infectious Disease • Myocardial Infarction • Oncology

Tranylcypromine-Based LSD1 Inhibitors as Useful Agents to Reduce Viability of Schistosoma mansoni. (PubMed, ACS Infect Dis) - "Schistosoma infections remain a major public health issue mainly in tropical and subtropical regions. While Praziquantel is the primary treatment for schistosomiasis, its limitations include resistance development and poor efficacy against juvenile worms. Given the biological similarities between tumor and parasite-infected cells, LSD1 inhibitors─primarily explored as anticancer agents─have been investigated for their antiparasitic potential."

Journal • Infectious Disease • Oncology

Triflupromazine and tranylcypromine alleviate primary cisplatin resistance in lung adenocarcinoma by promoting LDHA-mediated AMBRA1 ubiquitination. (PubMed, Biochem Pharmacol) - "Importantly, we identified two LDHA inhibitors, triflupromazine (TRI) and tranylcypromine (TRA), that significantly improve cisplatin efficacy both in vitro and in vivo. These findings highlight a critical role of LDHA in promoting cisplatin resistance, and suggest that targeting LDHA may represent a promising therapeutic strategy for patients with advanced LUAD."

IO biomarker • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • AMBRA1 • BCL2 • CCND1 • LDHA

Consistent differential effects of bupropion and mirtazapine in major depression. (PubMed, J Affect Disord) - "Bupropion is most effective for hypersomnia, increased weight, increased appetite, or fatigue, while mirtazapine is preferable for insomnia, decreased weight, or decreased appetite. SV enables statistically rigorous, symptom-level differentiation using only treatment assignment, offering a scalable and clinically aligned framework for guiding antidepressant selection from individual clinical trials."

Journal • CNS Disorders • Depression • Fatigue • Insomnia • Major Depressive Disorder • Mood Disorders • Psychiatry • Sleep Disorder

The Combination of Two Small Molecules Improves Neurological Parameters and Extends the Lifespan of C3H Strain Female Mice. (PubMed, Brain Behav) - "Chemical cocktails like RepSox and tranylcypromine (TCP) may induce beneficial age-related changes without the risks of full reprogramming...Histological findings revealed localized adaptive changes rather than major toxic effects. These results suggest that the combination of RepSox and TCP exerts protective effects on aging phenotypes and may potentially slow systemic aging processes in C3H mice."

Journal • Preclinical • Osteoporosis • Rheumatology

Atypical Antipsychotics in Mood and Other Disorders: Are We Too Quick on the Draw? - A Panel Discussion (APA 2025) - "Following the 1989 advent of SGAs when clozapine was launched, these medications began their triumphant march across the pages of the DSM: prescribed on-label for Schizophrenia, Schizoaffective Disorder, Bipolar Disorder, Major Depression augmentation, irritability associated with Autism Spectrum Disorder, suicidal risk reduction; off-label for PTSD, sleep disorders, ADHD, Tourettes Disorder, OCD, panic disorder, eating disorders, and both on label and off label - depending on which SGA - agitation associated with Alzheimer's.`...In the 1960s and 70s there were several formulations which combined first generation antipsychotics with antidepressants in a single pill (e.g., amitriptyline+perphenazine, tranylcypromine+trifluoperazine.) Although these combinations are still available, they seemed to fall out of favor in the 1980s, perhaps as a result of increasing attention to the challenge of tardive dyskinesia and the increasing faith in newer antidepressants. (We..."

ADHD (Impulsive Aggression) • Alzheimer's Disease • Attention Deficit Hyperactivity Disorder • Autism Spectrum Disorder • Bipolar Disorder • CNS Disorders • Depression • Genetic Disorders • Major Depressive Disorder • Mood Disorders • Movement Disorders • Post-traumatic Stress Disorder • Psychiatry • Schizophrenia • Sleep Disorder • Tourette Syndrome