dextromethorphan / Generic mfg. - LARVOL DELTA

Intracellular Crosstalk Between NMDA and Sigma-1 Receptors: A Novel Mechanistic Insight Relevant to Neuropsychiatric Pharmacotherapy. (PubMed, Cells) - "Experimental data demonstrate that pharmacological agents initially characterized as NMDAR antagonists-such as ketamine, dextromethorphan, and memantine-also interact with σ1R, suggesting that their therapeutic efficacy may arise from coordinated modulation of both receptor systems. These findings collectively indicate that the σ1R is a key regulatory element enabling proper NMDAR function and that disruption of this interaction may contribute to excitatory imbalance implicated in the pathophysiology of neuropsychiatric disorders. Recognizing the σ1R-NMDAR crosstalk as an integrated signaling axis may thus inform the development of dual-target therapeutic strategies aimed at improving neuronal resilience and clinical outcomes in psychiatric and neurodegenerative diseases."

Journal • Review • Addiction (Opioid and Alcohol) • B Cell Lymphoma • CNS Disorders • Lymphoma • Mental Retardation • Oncology • Psychiatry • BCL2

Adult U.S. Poison Center Exposure Case Trends Involving Nonprescription Dextromethorphan Amid the COVID-19 Pandemic: a Quasi-experimental Interrupted Time Series Study. (PubMed, J Med Toxicol) - "Nonprescription DXM exposures declined sharply at the pandemic's onset, with unintentional-therapeutic errors subsequently rebounding - especially among females - surpassing pre-pandemic levels toward the end of the pandemic's public health emergency declaration, while intentional exposures showed modest changes following initial declines. These findings underscore the need for targeted prevention strategies regarding inappropriate nonprescription DXM use and enhanced medication safety messaging during prolonged public health crises."

Journal • Cough • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Robust graphene oxide composite aerogel for micro solid-phase extraction of methorphan enantiomers from biological matrices. (PubMed, J Chromatogr A) - "Methorphan exists as two optically active enantiomers, levomethorphan (LVM) and dextromethorphan (DXM)...The spiked recoveries in urine and nail samples ranged from 81.6% to 108.4%, and matrix effects ranged from 83.3% to 105.7%. This method provides a facile, rapid, green and sensitive analytical strategy for the trace analysis of methorphan enantiomers in complex biological matrices."

Journal

LIFE-THREATENING SEROTONIN TOXICITY FROM ISOLATED DEXTROMETHORPHAN OVERDOSE (CHEST 2026) - No abstract available

Critical care

Evaluation of the Effect of Cendakimab on the Pharmacokinetics of CYP Probe Drugs in Patients With Eosinophilic Esophagitis. (PubMed, Clin Transl Sci) - "Patients received a cocktail of probe substrates (caffeine 200 mg, warfarin 10 mg + vitamin K 10 mg, omeprazole 40 mg, dextromethorphan 30 mg, midazolam 5 mg) for cytochrome P450 1A2, 2C9, 2C19, 2D6, and 3A in two sequential periods, separated by 16 weeks of cendakimab treatment. No clinically relevant changes in laboratory tests, vital signs, or electrocardiograms were observed. Cendakimab had no clinically meaningful effects on cytochrome P450 enzyme activities and was generally safe and well tolerated with or without probe substrates in adults with active eosinophilic esophagitis."

Journal • PK/PD data • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology • Inflammation • IL13

Severe Serotonin Syndrome With Acute Respiratory Failure Following Ayahuasca and Dextromethorphan Use: A Case Report. (PubMed, Cureus) - "Ayahuasca is a psychoactive botanical brew originating from Amazonian ceremonial traditions, containing monoamine oxidase inhibitors (MAOIs) derived from Banisteriopsis caapi and N,N-dimethyltryptamine from Psychotria viridis or Diplopterys cabrerana. Severe SS attributable to ayahuasca is rarely documented, and to our knowledge this is the first report of ayahuasca combined with over-the-counter DXM and diphenhydramine producing SS severe enough to cause acute respiratory failure. This case highlights the life-threatening potential of combining ayahuasca with commonly available serotonergic medications and underscores the need for clinician awareness of these interactions."

Journal • CNS Disorders • Critical care • Respiratory Diseases

Demographic characteristics and psychosocial backgrounds of patients with dextromethorphan overdose in Japan: A multicenter prospective observational study. (PubMed, PCN Rep) - "On comparing the younger group aged 10-19 years (n = 38) and the older group aged ≥20 years (n = 40), the number of patients who indicated that the source of information on dextromethorphan overdose was internet searches in the former group (19, 50.0%) was significantly higher than that in the latter group (10, 25.0%). Dextromethorphan overdose predominantly involved young women, and drug-related problems were common."

Journal • Observational data

A minimal three-arm oral regimen for healthspan: mechanistic alignment with transcriptomic signals from a large parental-lifespan GWAS. (PubMed, Front Aging) - "Building on those directional findings, this short communication proposes a minimal three-arm oral regimen with unequal evidentiary weight: first, the Cheung Glutamatergic Regimen, consisting of low-dose dextromethorphan potentiated by a CYP2D6 inhibitor together with piracetam and L-glutamine, as an exploratory adjunct aimed at preserving residual functional connectivity; second, daily nicotinamide mononucleotide and N-acetylcysteine with pulsed senolytics for NAD + salvage and senescence modulation; and third, GLP-1 receptor agonism for metabolic reprogramming. The regimen is fully oral, uses conservative dosing, and draws on prior therapeutic or human-exposure data, although the proposed combination has no established safety profile. Although direct combination data are lacking and the foundational TWAS remains a preprint, the components show plausible but uneven mechanistic alignment with the TWAS signals and may justify carefully designed, safety-focused pilot..."

Journal

A Staged Translational Framework for Evaluating Oral Glutamatergic and Senescence-Modulating Strategies in Treatment-Resistant Depression. (PubMed, Drug Des Devel Ther) - "The central hypothesis is that an oral dextromethorphan-CYP2D6-inhibitor-piracetam regimen could, if pharmacokinetically and clinically validated, initiate glutamatergic plasticity, whereas nicotinamide mononucleotide (NMN) plus N-acetylcysteine (NAC), followed only at a later stage by a candidate senescence-directed agent, could be evaluated for effects on the redox, bioenergetic, inflammatory, and cellular-aging context associated with response durability in a biomarker-enriched subset of unipolar TRD...Dasatinib plus quercetin is therefore positioned as a later-stage, specialist-supervised research probe rather than a routine psychiatric augmentation. No clinical role can yet be assigned to any proposed combination, and none should be used outside formal research protocols. The proposed development sequence prioritizes pharmacokinetic characterization, safety, target engagement, biomarker-defined subgroup selection, controlled efficacy testing, and independent..."

Journal • CNS Disorders • Depression • Mood Disorders • Psychiatry

Honey vs. pharmacological treatment for acute cough in children: a systematic review and meta-analysis of randomized controlled trials. (PubMed, Eur J Pediatr) - "While the primary analysis demonstrated comparable efficacy between interventions across most endpoints, except for child sleep quality, exploratory post-hoc sensitivity analyses revealed a potential signal of honey superiority across all outcomes. Although these findings should be regarded as hypothesis-generating rather than definitive, the potential clinical benefit, combined with the established risks of pediatric antitussives, supports honey as a promising, low-risk alternative."

Clinical • Journal • Retrospective data • Review • Cough • Pediatrics • Respiratory Diseases

Effect of Rivoceranib 200 mg Once Daily on the Pharmacokinetics of a Cocktail Probe Substrate of Cytochrome P450 Enzymes: A Phase I Trial in Healthy Volunteers. (PubMed, Clin Pharmacokinet) - P1 | "Rivoceranib 200 mg QD may substantially inhibit the metabolism of CYP2D6 substrates. Therefore, concomitant use of CYP2D6 substrate drugs with rivoceranib should be approached with caution, and dose adjustment of substrates of CYP2D6 may be necessary when co-administration cannot be avoided. Rivoceranib 200 mg QD may also exert weak inhibitory effects on the metabolism of CYP3A, CYP2C9, and CYP2C19 substrates. In such cases, close monitoring for substrate-related adverse reactions is recommended, particularly when toxicity is sensitive to increased exposures of these substrate drugs."

Journal • P1 data • PK/PD data • Hepatocellular Cancer • Oncology • Solid Tumor • CYP1A2 • CYP2C19 • CYP2C9 • CYP3A4

PEGASUS: A Study Investigating the Change in Metabolism Phenotype in Paediatric, Adolescent & Young Adults With Hodgkin or Non-Hodgkin Lymphoma. (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: Murdoch Childrens Research Institute | Trial completion date: Jul 2026 ➔ Nov 2026 | Trial primary completion date: Jul 2026 ➔ Nov 2026

Trial completion date • Trial primary completion date • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pediatrics

Aerogel Pore-Confined High-Loading MOF-199 for Micro-Solid-Phase Extraction of Methorphan Enantiomer in Biological Samples. (PubMed, J Sep Sci) - "Dextromethorphan is a widely used clinical antitussive, while its enantiomer, levomethorphan, is a controlled substance...Recoveries of dextro- and levo-methorphan from urine and hair samples were in the ranges of 88.9%-119.3% and 78.6%-115.7%, respectively. This method provides an effective strategy for the determination of methorphan enantiomers in biological samples, featuring rapid pretreatment, low organic solvent consumption, as well as facile operation."

Journal

Careful Consideration of the Use of Dextrothomorphan in Attenuated Non-Ketotic Hyperglycinemia (SSIEM 2026) - "Dextromethorphan, a known N-methyl-D-aspartate (NMDA) antagonist, was reported to improve seizures in a classical neonatal-onset case in 1992, and the two drugs have subsequently become a mainstay of treatment...There are recognised syndromes of abuse and withdrawal of the drug, and no conclusive evidence that it is effective in attenuating NKH. Hence, its use should be carefully considered in this situation, especially if there is no evidence of seizures."

CNS Disorders • Developmental Disorders • Epilepsy

Pharmacokinetic Drug-Drug Interactions of Imlunestrant in Healthy Female Participants of Nonchildbearing Potential. (PubMed, Clin Transl Sci) - "Participants tolerated imlunestrant at 200-800-mg doses, alone or with a CYP3A inhibitor (itraconazole), CYP3A inducer (carbamazepine), P-glycoprotein (P-gp) inhibitor (quinidine), and substrates of CYP2C8 (repaglinide), CYP2C19 (omeprazole), CYP2D6 (dextromethorphan), CYP3A (midazolam), P-gp (digoxin), and BCRP (rosuvastatin). Imlunestrant had no DDIs with CYP2C8 (repaglinide), CYP2C19 (omeprazole), and CYP3A4 (midazolam) substrates, or a P-gp inhibitor (quinidine), but weakly inhibited dextromethorphan (CYP2D6 substrate), digoxin (P-gp substrate), and rosuvastatin (BCRP substrate) clearance. Thus, considerations should be taken when imlunestrant is coadministered with strong CYP3A4 inhibitors, strong CYP3A4 inducers, and CYP2D6 and P-gp substrates where small changes in exposure may lead to toxicities."

Journal • PK/PD data • Breast Cancer • Constipation • Gastroenterology • Gastrointestinal Disorder • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Pain • Solid Tumor • CYP2C19 • ER • HER-2

Analysis of eight OTC drug components in postmortem dried blood spot samples by liquid chromatography-tandem mass spectrometry. (PubMed, Leg Med (Tokyo)) - "We combined the DBS method with liquid chromatography coupled with electrospray ionization-tandem mass spectrometry to quantify eight OTC drug components (apronal, caffeine, chlorpheniramine, dextromethorphan, diphenhydramine, diprophylline, noscapine, and promethazine). Comparison with our general practice method showed good positive correlations at the quantifiable concentrations of all drugs. Furthermore, when applied to an actual case, it was possible to diagnose death by drug poisoning, confirming the usefulness of this method."

Journal

Stability-Indicating RP-HPLC Determination of Acetylsalicylic Acid, Dextromethorphan Hydrobromide, Phenylephrine Bitartrate, and Chlorpheniramine Maleate in an Effervescent Tablet Formulation. (PubMed, J AOAC Int) - "This method employs ion-pairing at pH 2.0 optimized for the effervescent matrix and dual-wavelength detection for the quantification of actives and selected impurities. Fully validated per ICH Q2(R2), it demonstrates a clear stability-indicating capability and suitability for QC and stability studies of the evaluated effervescent tablet formulation."

Journal

Dextromethorphan-associated neurotoxicity with cerebellar edema (DANCE) syndrome. (PubMed, Clin Toxicol (Phila)) - "With supportive treatment and intravenous methylprednisolone, both patients recovered rapidly with no residual neurologic deficits. Therefore, this syndrome should be considered in the differential diagnosis at an early stage. There is a need to increase awareness among healthcare providers to avoid prescribing dextromethorphan-containing cough syrups to younger children."

Journal • CNS Disorders • Cough • Pediatrics • Respiratory Diseases

A Study to Investigate the Effect of Capivasertib on the Pharmacokinetics of Oral Dextromethorphan (CYP2D6 Substrate) in Healthy Participants (clinicaltrials.gov) - P1 | N=42 | Completed | Sponsor: AstraZeneca | Recruiting ➔ Completed

Trial completion

Establishment of a Novel Approach for Drug Abuse Monitoring and Its Application in Medical Institutions. (PubMed, Med Sci Monit) - "Antipyretic and analgesic drugs containing caffeine were abused in 4.11% of cases; dextromethorphan or Yumei tablets were involved in 3.42% of cases. Nitrous oxide abuse was identified in 2.05% of all monitored cases; affected patients were aged 17 to 25 years. CONCLUSIONS The proposed DAM approach was successfully implemented in a hospital setting and demonstrated feasibility for systematic monitoring of drug abuse in medical institutions."

Journal • Observational data • Retrospective data • CNS Disorders • Pain • Psychiatry • Substance Abuse

Differential Improvement in Obsessive Rumination and Fantasy Intrusions Versus Attachment-Related Emotional Dysregulation During Oral Glutamatergic Augmentation in a 16-Year-Old Adolescent. (PubMed, Cureus) - "A low-to-moderate-intensity Cheung glutamatergic regimen-like strategy was introduced, consisting of dextromethorphan, a CYP2D6-inhibiting antidepressant, and piracetam, with risperidone co-prescribed for fantasy-related cognitions, overvalued ideas, and obsessive instability. However, interpretation is limited by polypharmacy, risperidone titration, selective serotonin reuptake inhibitor (SSRI) effects, supportive care, natural symptom fluctuation, and the absence of formal obsessive-compulsive ratings or withdrawal/rechallenge. This case is best viewed as hypothesis-generating."

Journal • Anorexia • CNS Disorders • Depression • General Anxiety Disorder • Mood Disorders • Psychiatry • Sleep Disorder

CYP450-based reclassification of urinary metabolic ratio cutoffs for pain management and substance abuse treatment drugs. (PubMed, J Opioid Manag) - "These pairs include dextrorphan/dextromethorphan, oxymorphone/oxycodone, hydromorphone/hydrocodone, O-desmethyltramadol/tramadol, hydromorphone/-morphine, norbuprenorphine/buprenorphine, norfentanyl/-fentanyl, -noroxycodone/-oxycodone, norhydrocodone/hydrocodone, -7-aminoclonazepam/clonazepam, α-hydroxyalprazolam/alprazolam, norquetiapine/quetiapine, meprobamate/carisoprodol, N-desmethyltapentadol/tapentadol, norketamine/ketamine, -2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine/methadone, -desipramine/imipramine, and nortriptyline/amitriptyline. MR-derived phenotype classifications aligned with the phenotype frequencies reported in Zhu et al., indicating that population-level MR distributions reflect known CYP450 genetic variability. Incorporating CYP-specific cutoffs alongside traditional 95 percent RIs may improve identification of expected genetic metabolism, reduce misclassification, and enhance the interpretive accuracy of MR analysis in clinical UDT."

Journal • Pain • Substance Abuse • CYP2C19 • CYP2C9 • CYP3A4

AI-assisted versus manual sustainability assessment of a high-throughput LC-MS/MS method for psychotropic and OTC drugs of abuse in human plasma. (PubMed, Sci Rep) - "A rapid, sensitive, and selective LC-MSMS method was developed and validated for the quantification of dextromethorphan (DXM), pseudoephedrine (PSE), olanzapine (OLA), and fluoxetine (FLU) in human plasma. This study represents a novel application of artificial intelligence (AI)-assisted evaluation, utilizing a universally accessible model to assess the greenness and whiteness of the proposed LC-MS/MS method through the Auto-AGREE and Auto-RGB 12 frameworks. The AI-generated assessments demonstrated high agreement with traditional metrics, highlighting the potential of AI tools to provide rapid and objective holistic sustainability evaluations for the global analytical community."

Journal

Effects of Shuganning Injection on enzymatic activities of cytochrome P450 and its interaction with bicyclol (PubMed, Zhongguo Zhong Yao Za Zhi) - "In vivo experiments demonstrated that SGN significantly altered the pharmacokinetic parameters of caffeine, dextromethorphan, midazolam, and omeprazole in rats, primarily characterized by a marked increase in the area under the curve(AUC)(P<0.05) and a significant decrease in clearance(CL)(P<0.05). By inhibiting CYP2C19 and CYP3A2, SGN slowed down the metabolic clearance of BIC, leading to elevated plasma drug concentrations. These findings suggest a potential risk of increased drug exposure when SGN is used in combination with BIC in clinical practice."

Journal • CYP1A2 • CYP2C19 • CYP2C9 • CYP2E1 • CYP3A4

Optimized Oral Glutamatergic Augmentation in Refractory Home-Dominant Contamination Obsessive-Compulsive Disorder With Somatic, Affective, and Motivational Features: A Case Report of Incremental Functional Gains. (PubMed, Cureus) - "The Cheung glutamatergic regimen has been proposed as an oral, low-cost, ketamine-informed glutamatergic strategy using dextromethorphan, CYP2D6 inhibition, piracetam, and L-glutamine to modulate glutamatergic plasticity...A glutamatergic-oriented augmentation strategy was used as part of a complex, evolving regimen built around dextromethorphan, piracetam, and later L-glutamine, with pharmacokinetic potentiation via CYP2D6-inhibiting antidepressants, including fluoxetine, bupropion, and later low-dose paroxetine. Low-dose risperidone, clomipramine, pregabalin, propranolol, cyproheptadine, and other symptom-focused adjuncts were used and adjusted according to response and tolerability...The response was incomplete but clinically meaningful, especially in affective, somatic, motivational, and functional domains. Larger controlled studies are needed, and home-targeted exposure-based work remains essential."

Journal • CNS Disorders • Fatigue • General Anxiety Disorder • Mood Disorders • Obsessive-Compulsive Disorder • Psychiatry • Suicidal Ideation