RARE DISEASE
Methanol poisoning
Methanol poisoning
Methanol poisoning
Drug discovery
2
drugs
With orphan designations
Overview
Methanol Poisoning Overview
Methanol toxicity arises from its metabolism to formic acid, causing severe metabolic acidosis, visual disturbances (often permanent blindness), and multisystem organ failure [6][10][12]. Symptoms manifest after 12–24 hours, including gastrointestinal distress, CNS depression, and metabolic derangements [6][12]. Critical interventions involve antidotes (fomepizole or ethanol) to inhibit alcohol dehydrogenase, sodium bicarbonate for acidosis, and hemodialysis for toxin removal [1][10][13]. Mortality exceeds 20% in untreated cases, with survivors frequently experiencing long-term neurological or visual sequelae [4][17].
Population
Primarily affects adults in low-resource settings via contaminated alcohol consumption; outbreaks disproportionately impact manual laborers and marginalized communities [2][14].
Incidence peaks during mass poisoning events (e.g., 2024 Tamil Nadu outbreak: 225 cases, 65 deaths) [2][17].
Intentional ingestion accounts for 44% of U.S. cases, often involving younger populations [4].
Burden
Mortality: 6.5% in hospitalized U.S. cases; exceeds 40% in global outbreaks without rapid treatment [4][17].
Morbidity: Permanent blindness in 8–30% of survivors; renal/respiratory failure in 20–40% [4][6][10].
Economic impact: Mean U.S. hospitalization costs reach $43,222 per patient; outbreaks strain healthcare systems [4][17].
Categories: rare disorders due to toxic effects
Research Papers
597 drug discovery papers about Methanol poisoning, with 1 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
597 drug discovery papers about Methanol poisoning, with 1 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
proteins
2025-07-18 | Clinical and laboratory prognostic factors associated with methanol toxicity outcomes in patients at Tabriz Sina Hospital: A retrospective study.
IntroductionMethanol toxicity is a significant health concern with potentially severe outcomes. This study aimed to investigate the prognostic factors of patients with methanol toxicity referred to Tabriz Sina Hospital.MethodsA descriptive-analytical retrospective study was conducted in methanol toxicity patients admitted in Tabriz Sina Hospital since 2019 to 2021. Demographic characteristics and management methods were extracted from the patients' medical records.ResultsPatients were predominantly male (91.3%) with a median age of 30-40 years. Winter accounted for 48.7% of cases. Coma (OR = 8.0, 95% CI: 3.2-19.9) and arrhythmia (OR = 5.5, 2.0-15.1) at admission, pH <7.1 (OR = 4.2, 2.0-8.9), elevated creatinine (OR = 1.3/mg/dL, 1.1-1.6), opiate co-use (OR = 2.8, 1.2-6.5), and delayed ethanol therapy (>3 h, OR = 2.3, 1.1-4.8) independently increased mortality risk. Bicarbonate, Eprex, and methylprednisolone reduced complications. Time from ingestion to admission (48-72 h) did not affect mortality, but delayed hemodialysis initiation worsened outcomes.ConclusionEarly presentation and providing early therapeutic modalities have a significant impact on the mortality rate and the patients' outcome.
2024-11-27 | Effect of elamipretide and methylprednisolone treatment on optic nerve, retina and brain damage in a methanol poisoning model: biochemical and histopathological evaluation.
This study aimed to biochemically and histopathologically evaluate the protective and therapeutic effects of elamipretide and methylprednisolone on methanol poisoning-induced brain, optic nerve, and retinal toxicity. In this study, 40 male Wistar Albino rats were divided into six groups: healthy control (HC), methotrexate (MTX, 0.3 mg/kg/d for 7 d), methotrexate + methanol (MTX-M, 0.3 mg/kg/d for 7 d + methanol 3 g/kg on Day 8), methotrexate + methanol + methylprednisolone (MTX-M-MPZ, 0.3 mg/kg/d for 7 d + methanol 3 g/kg on Day 8 + MPZ 1 mg/kg/d for 3 d), methotrexate + methanol + elamipretide (MTX-M-E, 0.3 mg/kg/d for 7 d + methanol 3 g/kg on Day 8 + elamipretide 5 mg/kg/d for 3 d), and methotrexate + methanol + methylprednisolone + elamipretide (MTX-M-MPZ-E, 0.3 mg/kg/d for 7 d + methanol 3 g/kg on Day 8 + MPZ 1 mg/kg/d + Elamipretide 5 mg/kg/d for 3 d). The rats were euthanized 8 h after the last drug administration. Histopathological and biochemical evaluations were performed on serum, caudatoputamen, and ocular tissues. Retinal degeneration was assessed using a scoring system where higher scores indicate less degeneration, with a score of 5 representing normal structure and 1 reflecting severe degeneration. In the MTX-M-MPZ-E group, the retinal degeneration score was higher than in MTX-M group (p = 0.002). The apoptosis index in the retina was highest in MTX-M group, while it was lower in MTX-M-MPZ-E group compared to MTX-M group (p = 0.018). In addition, the apoptosis index in the caudatoputamen was lower in MTX-M-MPZ-E group compared to MTX-M group (p = 0.009). Combined elamipretide and methylprednisolone treatment improved optic nerve and retinal degeneration, reduced neuronal degeneration in the caudatoputamen, decreased oxidative stress and lipid peroxidation, and reduced apoptosis in the retina and caudatoputamen.
2024-05-28 | Methanol Induced Optic Neuropathy: Molecular Mysteries, Public Health Perspective, Clinical Insights and Treatment Strategies.
Methanol-induced optic neuropathy (MION) represents a critical public health issue, particularly prevalent in lower socioeconomic populations and regions with restricted alcohol access. MION, characterized by irreversible visual impairment, arises from the toxic metabolization of methanol into formaldehyde and formic acid, leading to mitochondrial oxidative phosphorylation inhibition, oxidative stress, and subsequent neurotoxicity. The pathogenesis involves axonal and glial cell degeneration within the optic nerve and potential retinal damage. Despite advancements in therapeutic interventions, a significant proportion of affected individuals endure persistent visual sequelae. The study comprehensively investigates the pathophysiology of MION, encompassing the absorption and metabolism of methanol, subsequent systemic effects, and ocular impacts. Histopathological changes, including alterations in retinal layers and proteins, Müller cell dysfunction, and visual symptoms, are meticulously examined to provide insights into the disease mechanism. Furthermore, preventive measures and public health perspectives are discussed to highlight the importance of awareness and intervention strategies. Therapeutic approaches, such as decontamination procedures, ethanol and fomepizole administration, hemodialysis, intravenous fluids, electrolyte balance management, nutritional therapy, corticosteroid therapy, and erythropoietin (EPO) treatment, are evaluated for their efficacy in managing MION. This comprehensive review underscores the need for increased awareness, improved diagnostic strategies, and more effective treatments to mitigate the impact of MION on global health.
2024-02-01 | The Adverse Reactions of Erythropoietin in Methanol Toxicity: A Descriptive Study
Background: Nowadays, erythropoietin is employed as a substitute therapy for eye ailments, particularly optic nerve damage induced by methanol toxicity. Despite its benefits, erythropoietin can have negative effects on blood factors. These effects may include thrombosis, stroke, seizures, and changes in hematological function. This study examined the adverse effects of erythropoietin on individuals suffering from optic neuropathy caused by methanol. Methods: This study was a prospective descriptive study at Loghman Hakim Hospital, Tehran City, Iran, in 2022. The study involved individuals who suffered from methanol poisoning and were administered erythropoietin twice a day for three days, with a dosage of 10000 units each time. Patients were examined up to 6 weeks after discharge in terms of increased hemoglobin levels, seizures, central vascular thrombosis, and heart attack or stroke. The data was analyzed by SPSS software, version 18. Results: The study comprised of 37 patients. No patient reported seizures, heart and cerebral strokes, and deep vein thrombosis except polycythemia. After being discharged from the hospital, the mean hemoglobin levels increased by 2.01% six weeks later compared to the levels measured during admission. Moreover, there was a 2.4% rise in hemoglobin levels six weeks after discharge when compared to the levels measured two weeks after being discharged. Conclusion: Using erythropoietin to treat optic neuropathy can improve vision, but it also carries the risk of increasing hemoglobin levels, which must be monitored closely in treated patients.
2023-03-01 | Intravenous plus intravitreal erythropoietin for management of methanol toxicity optic neuropathy: A case report and brief review
Methanol can inhibit cellular aerobic respiration pathway and causes cell hypoxia specially in optic neurons. Despite using many drugs, methanol-induced optic neuropathy (MION) still has a poor prognosis. Here we present a case of MION which is managed by a combination of intravenous and intravitreal erythropoietin in addition to corticosteroids.
small molecules
2026-07-31 | PdNi/N-C dodecahedra with surface-enriched Pd for efficient methanol electro-oxidation in alkaline media.
The methanol electrooxidation reaction (MOR) is a key anodic process in direct methanol fuel cells, yet its practical application remains hindered by several critical challenges, including the high cost and limited reserves of noble metal catalysts, severe CO poisoning of active sites, and insufficient long-term durability. Herein we report a PdNi/N-C catalyst derived from ZIF-8 dodecahedra, featuring Pd-enriched surfaces on a nitrogen-doped carbon support. The unique architecture ensures high Pd utilization while the PdNi alloying effect, combined with the presence of excess Ni nanoparticles, promotes the bifunctional mechanism to effectively mitigate CO poisoning and enhance reaction kinetics. The catalyst delivers a mass activity of 6.20 A mg-1Pd for the MOR, which is 6.75 times higher than that of commercial Pd/C, along with significantly improved stability during accelerated durability tests. This work highlights the importance of support morphology and Pd surface enrichment in bimetallic catalyst design, offering a promising strategy for developing high-performance and cost-effective anode catalysts for direct methanol fuel cells.
2026-07-21 | Lattice-Expanded Pt Overlayer with Surface Pb Modulation on a PtPb Alloy toward High-Efficiency Methanol Oxidation.
The sluggish kinetics and poor stability of the methanol oxidation reaction (MOR) in platinum (Pt)-based materials are primarily attributed to the strong adsorption of carbon monoxide (CO), which hinders the application of direct methanol fuel cells (DMFCs). Herein, we demonstrate that a PtPb core/tensile strained Pt shell with surface Pb-modified nanosheets (PtPb@Pt@Pb NSs) alleviates the CO poisoning of Pt, thereby enhancing its MOR activity and durability. Benefiting from the lattice expansion of Pt and the surface Pb, PtPb@Pt@Pb NSs/C exhibits superior MOR activity and durability. Corresponding experiments and density functional theory (DFT) calculations reveal that both the lattice-stretched Pt shell and the surface Pb enhance the OH adsorption for oxidative removal of the adsorbed CO and weaken CO binding on Pt. Meanwhile, the synergistic effect between the tensile-strained Pt and surface Pb layer lowers the reaction energy barrier of the rate-determining step for MOR, thereby endowing it with excellent activity.
2026-07-09 | Carbon-Confined FeCo@Pt Nanocatalysts Derived from Metal-Organic Frameworks for Pt-Economical, High-Performance, and CO-Tolerant Methanol Electrooxidation.
A major challenge in developing direct methanol fuel cells (DMFCs) is to design Pt-based electrocatalysts that reduce Pt consumption while maintaining high activity, durability, and resistance to carbonaceous poisoning during the methanol oxidation reaction (MOR). Herein, a metal-organic framework (MOF)-derived confinement strategy is proposed to construct FeCo@Pt core-shell nanocatalysts embedded in nitrogen-doped porous carbon (NPC). This architecture integrates three key functions within one catalyst platform: an FeCo alloy core for electronic modulation of the Pt shell, a Pt-rich surface for efficient methanol oxidation, and an NPC matrix for nanoparticle confinement, structural stabilization, and accelerated mass/charge transport. Benefiting from this cooperative design, the optimized FeCo@Pt/NPC-T800-X15-t20 catalyst delivered a mass activity of 663.84 mA mgPt-1, which was 1.92 times that of commercial Pt/C. It maintained a current density 5.81 times higher than that of Pt/C after 3600 s of operation. CO-stripping measurements further revealed a 66 mV negative shift in the CO oxidation peak, indicating enhanced oxidative removal of CO-like intermediates. Moreover, in situ attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) provided direct mechanistic evidence for the enhanced formation of OHads species, the generation of C-OH and *COOH intermediates, and the suppression of the accumulation of linearly adsorbed CO on Pt sites during MOR. These results demonstrate that the FeCo core facilitates the formation and spillover of oxygenated species, while the electronic interaction between FeCo and Pt weakens CO adsorption, thereby accelerating COads oxidation and improving poisoning resistance. This work highlights the effectiveness of coupling alloy-core modulation, Pt-shell utilization, and MOF-derived carbon confinement for developing Pt-economical, CO-tolerant, and durable MOR electrocatalysts.
2026-07-08 | Macro- andMesoporous Graphene-MXene ArchitecturesDecorated with Rhodium Nanocrystals for Methanol Oxidation Electrocatalysis
The development of advanced platinum-alternative anode catalysts with high catalytic activity and strong CO poison tolerance is of great significance to break through the technical bottleneck of the direct methanol fuel cell. Herein, we report the spatial construction of a rhodium-decorated three-dimensional macro- and mesoporous architecture built from holey graphene and holey Ti3C2Tx MXene (Rh/HG-HMX) through a combined oxidative-etching and solvothermal coassembly process. Such an exquisite structural design not only fully exposes the internal catalytically active sites as well as improves the mass transfer efficiency of reactants and products, but also affords strong interfacial interactions between metallic Rh and HG-HMX matrix to optimize their electronic structure, thus resulting in significant synergistic catalytic effects. Accordingly, the as-derived Rh/HG-HMX architecture exhibits excellent electrocatalytic methanol oxidation abilities in terms of a large electrochemically active surface area of 171.5 m2·g–1, a high mass activity of 2082.0 mA·mg–1, and dependable long-term durability, far exceeding those of traditional graphene and MXene-supported Rh catalysts as well as commercial Pt/C and Pd/C catalysts.
2026-07-08 | Macro- and Mesoporous Graphene-MXene Architectures Decorated with Rhodium Nanocrystals for Methanol Oxidation Electrocatalysis.
The development of advanced platinum-alternative anode catalysts with high catalytic activity and strong CO poison tolerance is of great significance to break through the technical bottleneck of the direct methanol fuel cell. Herein, we report the spatial construction of a rhodium-decorated three-dimensional macro- and mesoporous architecture built from holey graphene and holey Ti3C2Tx MXene (Rh/HG-HMX) through a combined oxidative-etching and solvothermal coassembly process. Such an exquisite structural design not only fully exposes the internal catalytically active sites as well as improves the mass transfer efficiency of reactants and products, but also affords strong interfacial interactions between metallic Rh and HG-HMX matrix to optimize their electronic structure, thus resulting in significant synergistic catalytic effects. Accordingly, the as-derived Rh/HG-HMX architecture exhibits excellent electrocatalytic methanol oxidation abilities in terms of a large electrochemically active surface area of 171.5 m2·g-1, a high mass activity of 2082.0 mA·mg-1, and dependable long-term durability, far exceeding those of traditional graphene and MXene-supported Rh catalysts as well as commercial Pt/C and Pd/C catalysts.
cell therapies
2021-11-02 | Successful Kidney Transplant From a Brain Stem-Dead Donor Due To Lethal Methanol Poisoning.
Kidney replacement is the best treatment modality for chronic renal failure; however,the greatest obstacle for transplant is the scarce number of donor organs. In the United States and Europe, less than 1% of organs for transplant are provided from patients with lethal poisoning. In this paper, we present a successful kidney transplant from a donor with methanol poisoning. A 38-year-old-man who had methanol poisoning developed brain stem death after unsuccessful treatment and was a candidate to be a kidney donor for transplant to a 27-year-old male patient with chronic renal failure. Three weeks after kidney transplant, the recipient was discharged with good kidney function. We suggest that it may be possible to consider lethal methanol poisoning for kidney donation.
2005-01-04 | Flux Analysis Uncovers Key Role of Functional Redundancy in Formaldehyde Metabolism
Genome-scale analysis of predicted metabolic pathways has revealed the common occurrence of apparent redundancy for specific functional units, or metabolic modules. In many cases, mutation analysis does not resolve function, and instead, direct experimental analysis of metabolic flux under changing conditions is necessary. In order to use genome sequences to build models of cellular function, it is important to define function for such apparently redundant systems. Here we describe direct flux measurements to determine the role of redundancy in three modules involved in formaldehyde assimilation and dissimilation in a bacterium growing on methanol. A combination of deuterium and (14)C labeling was used to measure the flux through each of the branches of metabolism for growth on methanol during transitions into and out of methylotrophy. The cells were found to differentially partition formaldehyde among the three modules depending on the flux of methanol into the cell. A dynamic mathematical model demonstrated that the kinetic constants of the enzymes involved are sufficient to account for this phenomenon. We demonstrate the role of redundancy in formaldehyde metabolism and have uncovered a new paradigm for coping with toxic, high-flux metabolic intermediates: a dynamic, interconnected metabolic loop.
2004-11-01 | Successful bilateral lung transplantation from a methanol-poisoned donor
The shortage of suitable organ donors is an important limiting factor that is making the evaluation of marginal donors necessary and, consequently, allowing expansion of standard donor criteria for organ removal. Lung procurement after methanol poisoning is anecdotal; in fact, there is only one published case in literature and that case showed a successful outcome. In this report, we describe a case of lung donation from a previously healthy individual who died from methanol poisoning. Both lungs were successfully implanted to a 20-year-old man who suffered from cystic fibrosis. This case report is new evidence that lung transplantation from methanol-poisoned donors may be safely performed with a good outcome.
2002-06-01 | Accreditation of skin from a methanol-poisoned victim for banking and grafting
Background. Acute poisoning is a contraindication for organ and tissue donation. In this study the suitability of skin from a methanol-poisoned (MP) donor for future grafting and keratinocytes culturing was investigated. Methods. A patient was admitted with a methanol blood level of 2.7 mg/mL, which became undetectable after 4 days of treatment with 4-methylpyrazole (fomepizole). Upon declared brain death and family consent, organs and skin were harvested. For approving MP skin for grafting, the following parameters were studied: viability and plating efficiency of MP keratinocytes, integrity of MP skin after cryopreservation, and its performance as xenografts on wounds in a pig model. Nonpoisoned (NP) controls included skin of matching age, cryopreservation period, and NP keratinocytes. Results. No significant differences were observed for any parameter between NP and MP samples. Furthermore, in vitro exposure of NP keratinocytes and fibroblasts to <10 mg/mL methanol inhibited their growth by <20%, with an extrapolated LD50 of 100 mg/mL. A parallel exposure to formaldehyde, a spontaneous metabolite of methanol, yielded LD50 of 20 μg/mL and eradication of viability at 300 μg/mL. Conclusions. These results indicate that skin from a carefully monitored MP donor is suitable for banking toward massive burns and skin losses. This methodology may be applied to approve skin harvested from other types of poisoned donors for banking and future grafting.
2001-04-01 | Successful cardiac transplantation with methanol or carbon monoxide-poisoned donors
Background. Patients succumbing to methanol or carbon monoxide poisoning are usually rejected for heart donation. Increasing demand for donors has lead to the expansion of acceptance criteria and increased use of the marginal donor.Methods. We transplanted hearts from donors who had had methanol intoxication in three cases and carbon monoxide exposure in two cases. Standard donor evaluation criteria and transplantation techniques were used.Results. All of the transplants were successful. Three of the recipients required significant inotropic support for a few days postoperatively; however, all of the hearts functioned well over the intermediate and long term. Two recipients (1 from each group) died of complications other than heart failure (1.5 and 2 years postoperatively).Conclusions. Successful heart transplantation can be achieved using the hearts from patients succumbing to methanol or carbon monoxide poisoning. Routine evaluation of cardiac function and myocardial damage is adequate for screening these donors. Hearts from methanol-poisoning victims may require longer inotropic support postoperatively before complete recovery, but can provide excellent long-term function and results.
oligonucleotides
2025-12-29 | Clinical Indicators of Hemodialysis and Mortality in Methanol Poisoning: A Retrospective Analysis.
Methanol poisoning is a severe medical emergency associated with high morbidity and mortality. Methanol poisoning leads to metabolic acidosis, visual disturbances, and central nervous system complications. Early diagnosis and timely treatment, including hemodialysis, are critical in improving outcomes. This study aimed to evaluate the clinical and laboratory predictors of mortality and the need for hemodialysis in methanol poisoning patients. It also sought to establish cutoff values for critical parameters that influence clinical decisions. A single-center retrospective cross-sectional study was conducted on patients over 18 years of age with suspected methanol poisoning between 2010 and 2022. Demographic, clinical, and laboratory data were collected and analyzed. Predictive parameters for mortality and hemodialysis were identified using Receiver Operating Characteristic (ROC) analysis. Sixty-four patients were included, with a mean age of 47.7 years and 92.2% being male. Mortality occurred in 29.7% of patients. ROC analysis identified a serum pH cutoff of ≤7.08 for mortality prediction (AUC: 0.894, P<0.001) and ≤7.315 for predicting the need for hemodialysis (AUC: 0.891, P<0.001). Serum bicarbonate levels were significant predictors, with a cutoff of ≤8.45 for mortality (AUC: 0.820, P<0.001) and ≤15.55 for hemodialysis (AUC: 0.883, P<0.001). Elevated lactate levels (cutoff ≥3.67 mmol/L) and an anion gap ≥27.25 were also strong predictors of mortality. Early recognition of critical parameters such as serum pH, sodium bicarbonate, lactate, and anion gap are essential in managing methanol poisoning.
2022-12-27 | MicroRNA-124 modulates neuroinflammation in acute methanol poisoning rats via targeting Krüppel-like factor-6.
Microglia activation-stimulated neuroinflammation exerts functionally in neurodegenerative diseases like brain injury. Acute methanol poisoning (AMP) is a crucial cause of death and morbidity that possibly leads to neuroinflammation. Studies have manifested that miRNAs can modulate microglia activation to mediate neuroinflammation. Nevertheless, the role of miR-124 in AMP-stimulated neuroinflammation is uncertain. This research was to explore the action of miR-124 in AMP-stimulated neuroinflammation and its molecular mechanism. The study findings indicated that AMP accelerated microglia activation and stimulated inflammation and oxidative stress in brain tissue of rats. MiR-124 expression was lowered in AMP rats, while KLF6 expression was elevated. Elevated miR-124 or repressed KLF6 increased the number of CD206+ cells and decreased the number of CD68+ cells, as well as restrained inflammation and NF-κB phosphorylation and induced superoxide dismutase, Nrf2/HO-1, and M2 polarization. MiR-124 modulated microglia activation via targeting KLF6. AMP repressed neuronal viability and enhanced neuronal apoptosis. Suppression of miR-124 further promoted AMP-induced damage to neurons, while inhibition of KLF6 turned around this phenomenon. Anyway, our study demonstrated that miR-124 accelerates M2 polarization via targeting KLF6 to ameliorate AMP-stimulated neuronal damage.
proteins
2025-07-18 | Clinical and laboratory prognostic factors associated with methanol toxicity outcomes in patients at Tabriz Sina Hospital: A retrospective study.
IntroductionMethanol toxicity is a significant health concern with potentially severe outcomes. This study aimed to investigate the prognostic factors of patients with methanol toxicity referred to Tabriz Sina Hospital.MethodsA descriptive-analytical retrospective study was conducted in methanol toxicity patients admitted in Tabriz Sina Hospital since 2019 to 2021. Demographic characteristics and management methods were extracted from the patients' medical records.ResultsPatients were predominantly male (91.3%) with a median age of 30-40 years. Winter accounted for 48.7% of cases. Coma (OR = 8.0, 95% CI: 3.2-19.9) and arrhythmia (OR = 5.5, 2.0-15.1) at admission, pH <7.1 (OR = 4.2, 2.0-8.9), elevated creatinine (OR = 1.3/mg/dL, 1.1-1.6), opiate co-use (OR = 2.8, 1.2-6.5), and delayed ethanol therapy (>3 h, OR = 2.3, 1.1-4.8) independently increased mortality risk. Bicarbonate, Eprex, and methylprednisolone reduced complications. Time from ingestion to admission (48-72 h) did not affect mortality, but delayed hemodialysis initiation worsened outcomes.ConclusionEarly presentation and providing early therapeutic modalities have a significant impact on the mortality rate and the patients' outcome.
2024-11-27 | Effect of elamipretide and methylprednisolone treatment on optic nerve, retina and brain damage in a methanol poisoning model: biochemical and histopathological evaluation.
This study aimed to biochemically and histopathologically evaluate the protective and therapeutic effects of elamipretide and methylprednisolone on methanol poisoning-induced brain, optic nerve, and retinal toxicity. In this study, 40 male Wistar Albino rats were divided into six groups: healthy control (HC), methotrexate (MTX, 0.3 mg/kg/d for 7 d), methotrexate + methanol (MTX-M, 0.3 mg/kg/d for 7 d + methanol 3 g/kg on Day 8), methotrexate + methanol + methylprednisolone (MTX-M-MPZ, 0.3 mg/kg/d for 7 d + methanol 3 g/kg on Day 8 + MPZ 1 mg/kg/d for 3 d), methotrexate + methanol + elamipretide (MTX-M-E, 0.3 mg/kg/d for 7 d + methanol 3 g/kg on Day 8 + elamipretide 5 mg/kg/d for 3 d), and methotrexate + methanol + methylprednisolone + elamipretide (MTX-M-MPZ-E, 0.3 mg/kg/d for 7 d + methanol 3 g/kg on Day 8 + MPZ 1 mg/kg/d + Elamipretide 5 mg/kg/d for 3 d). The rats were euthanized 8 h after the last drug administration. Histopathological and biochemical evaluations were performed on serum, caudatoputamen, and ocular tissues. Retinal degeneration was assessed using a scoring system where higher scores indicate less degeneration, with a score of 5 representing normal structure and 1 reflecting severe degeneration. In the MTX-M-MPZ-E group, the retinal degeneration score was higher than in MTX-M group (p = 0.002). The apoptosis index in the retina was highest in MTX-M group, while it was lower in MTX-M-MPZ-E group compared to MTX-M group (p = 0.018). In addition, the apoptosis index in the caudatoputamen was lower in MTX-M-MPZ-E group compared to MTX-M group (p = 0.009). Combined elamipretide and methylprednisolone treatment improved optic nerve and retinal degeneration, reduced neuronal degeneration in the caudatoputamen, decreased oxidative stress and lipid peroxidation, and reduced apoptosis in the retina and caudatoputamen.
2024-05-28 | Methanol Induced Optic Neuropathy: Molecular Mysteries, Public Health Perspective, Clinical Insights and Treatment Strategies.
Methanol-induced optic neuropathy (MION) represents a critical public health issue, particularly prevalent in lower socioeconomic populations and regions with restricted alcohol access. MION, characterized by irreversible visual impairment, arises from the toxic metabolization of methanol into formaldehyde and formic acid, leading to mitochondrial oxidative phosphorylation inhibition, oxidative stress, and subsequent neurotoxicity. The pathogenesis involves axonal and glial cell degeneration within the optic nerve and potential retinal damage. Despite advancements in therapeutic interventions, a significant proportion of affected individuals endure persistent visual sequelae. The study comprehensively investigates the pathophysiology of MION, encompassing the absorption and metabolism of methanol, subsequent systemic effects, and ocular impacts. Histopathological changes, including alterations in retinal layers and proteins, Müller cell dysfunction, and visual symptoms, are meticulously examined to provide insights into the disease mechanism. Furthermore, preventive measures and public health perspectives are discussed to highlight the importance of awareness and intervention strategies. Therapeutic approaches, such as decontamination procedures, ethanol and fomepizole administration, hemodialysis, intravenous fluids, electrolyte balance management, nutritional therapy, corticosteroid therapy, and erythropoietin (EPO) treatment, are evaluated for their efficacy in managing MION. This comprehensive review underscores the need for increased awareness, improved diagnostic strategies, and more effective treatments to mitigate the impact of MION on global health.
2024-02-01 | The Adverse Reactions of Erythropoietin in Methanol Toxicity: A Descriptive Study
Background: Nowadays, erythropoietin is employed as a substitute therapy for eye ailments, particularly optic nerve damage induced by methanol toxicity. Despite its benefits, erythropoietin can have negative effects on blood factors. These effects may include thrombosis, stroke, seizures, and changes in hematological function. This study examined the adverse effects of erythropoietin on individuals suffering from optic neuropathy caused by methanol. Methods: This study was a prospective descriptive study at Loghman Hakim Hospital, Tehran City, Iran, in 2022. The study involved individuals who suffered from methanol poisoning and were administered erythropoietin twice a day for three days, with a dosage of 10000 units each time. Patients were examined up to 6 weeks after discharge in terms of increased hemoglobin levels, seizures, central vascular thrombosis, and heart attack or stroke. The data was analyzed by SPSS software, version 18. Results: The study comprised of 37 patients. No patient reported seizures, heart and cerebral strokes, and deep vein thrombosis except polycythemia. After being discharged from the hospital, the mean hemoglobin levels increased by 2.01% six weeks later compared to the levels measured during admission. Moreover, there was a 2.4% rise in hemoglobin levels six weeks after discharge when compared to the levels measured two weeks after being discharged. Conclusion: Using erythropoietin to treat optic neuropathy can improve vision, but it also carries the risk of increasing hemoglobin levels, which must be monitored closely in treated patients.
2023-03-01 | Intravenous plus intravitreal erythropoietin for management of methanol toxicity optic neuropathy: A case report and brief review
Methanol can inhibit cellular aerobic respiration pathway and causes cell hypoxia specially in optic neurons. Despite using many drugs, methanol-induced optic neuropathy (MION) still has a poor prognosis. Here we present a case of MION which is managed by a combination of intravenous and intravitreal erythropoietin in addition to corticosteroids.
small molecules
2026-07-31 | PdNi/N-C dodecahedra with surface-enriched Pd for efficient methanol electro-oxidation in alkaline media.
The methanol electrooxidation reaction (MOR) is a key anodic process in direct methanol fuel cells, yet its practical application remains hindered by several critical challenges, including the high cost and limited reserves of noble metal catalysts, severe CO poisoning of active sites, and insufficient long-term durability. Herein we report a PdNi/N-C catalyst derived from ZIF-8 dodecahedra, featuring Pd-enriched surfaces on a nitrogen-doped carbon support. The unique architecture ensures high Pd utilization while the PdNi alloying effect, combined with the presence of excess Ni nanoparticles, promotes the bifunctional mechanism to effectively mitigate CO poisoning and enhance reaction kinetics. The catalyst delivers a mass activity of 6.20 A mg-1Pd for the MOR, which is 6.75 times higher than that of commercial Pd/C, along with significantly improved stability during accelerated durability tests. This work highlights the importance of support morphology and Pd surface enrichment in bimetallic catalyst design, offering a promising strategy for developing high-performance and cost-effective anode catalysts for direct methanol fuel cells.
2026-07-21 | Lattice-Expanded Pt Overlayer with Surface Pb Modulation on a PtPb Alloy toward High-Efficiency Methanol Oxidation.
The sluggish kinetics and poor stability of the methanol oxidation reaction (MOR) in platinum (Pt)-based materials are primarily attributed to the strong adsorption of carbon monoxide (CO), which hinders the application of direct methanol fuel cells (DMFCs). Herein, we demonstrate that a PtPb core/tensile strained Pt shell with surface Pb-modified nanosheets (PtPb@Pt@Pb NSs) alleviates the CO poisoning of Pt, thereby enhancing its MOR activity and durability. Benefiting from the lattice expansion of Pt and the surface Pb, PtPb@Pt@Pb NSs/C exhibits superior MOR activity and durability. Corresponding experiments and density functional theory (DFT) calculations reveal that both the lattice-stretched Pt shell and the surface Pb enhance the OH adsorption for oxidative removal of the adsorbed CO and weaken CO binding on Pt. Meanwhile, the synergistic effect between the tensile-strained Pt and surface Pb layer lowers the reaction energy barrier of the rate-determining step for MOR, thereby endowing it with excellent activity.
2026-07-09 | Carbon-Confined FeCo@Pt Nanocatalysts Derived from Metal-Organic Frameworks for Pt-Economical, High-Performance, and CO-Tolerant Methanol Electrooxidation.
A major challenge in developing direct methanol fuel cells (DMFCs) is to design Pt-based electrocatalysts that reduce Pt consumption while maintaining high activity, durability, and resistance to carbonaceous poisoning during the methanol oxidation reaction (MOR). Herein, a metal-organic framework (MOF)-derived confinement strategy is proposed to construct FeCo@Pt core-shell nanocatalysts embedded in nitrogen-doped porous carbon (NPC). This architecture integrates three key functions within one catalyst platform: an FeCo alloy core for electronic modulation of the Pt shell, a Pt-rich surface for efficient methanol oxidation, and an NPC matrix for nanoparticle confinement, structural stabilization, and accelerated mass/charge transport. Benefiting from this cooperative design, the optimized FeCo@Pt/NPC-T800-X15-t20 catalyst delivered a mass activity of 663.84 mA mgPt-1, which was 1.92 times that of commercial Pt/C. It maintained a current density 5.81 times higher than that of Pt/C after 3600 s of operation. CO-stripping measurements further revealed a 66 mV negative shift in the CO oxidation peak, indicating enhanced oxidative removal of CO-like intermediates. Moreover, in situ attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) provided direct mechanistic evidence for the enhanced formation of OHads species, the generation of C-OH and *COOH intermediates, and the suppression of the accumulation of linearly adsorbed CO on Pt sites during MOR. These results demonstrate that the FeCo core facilitates the formation and spillover of oxygenated species, while the electronic interaction between FeCo and Pt weakens CO adsorption, thereby accelerating COads oxidation and improving poisoning resistance. This work highlights the effectiveness of coupling alloy-core modulation, Pt-shell utilization, and MOF-derived carbon confinement for developing Pt-economical, CO-tolerant, and durable MOR electrocatalysts.
2026-07-08 | Macro- andMesoporous Graphene-MXene ArchitecturesDecorated with Rhodium Nanocrystals for Methanol Oxidation Electrocatalysis
The development of advanced platinum-alternative anode catalysts with high catalytic activity and strong CO poison tolerance is of great significance to break through the technical bottleneck of the direct methanol fuel cell. Herein, we report the spatial construction of a rhodium-decorated three-dimensional macro- and mesoporous architecture built from holey graphene and holey Ti3C2Tx MXene (Rh/HG-HMX) through a combined oxidative-etching and solvothermal coassembly process. Such an exquisite structural design not only fully exposes the internal catalytically active sites as well as improves the mass transfer efficiency of reactants and products, but also affords strong interfacial interactions between metallic Rh and HG-HMX matrix to optimize their electronic structure, thus resulting in significant synergistic catalytic effects. Accordingly, the as-derived Rh/HG-HMX architecture exhibits excellent electrocatalytic methanol oxidation abilities in terms of a large electrochemically active surface area of 171.5 m2·g–1, a high mass activity of 2082.0 mA·mg–1, and dependable long-term durability, far exceeding those of traditional graphene and MXene-supported Rh catalysts as well as commercial Pt/C and Pd/C catalysts.
2026-07-08 | Macro- and Mesoporous Graphene-MXene Architectures Decorated with Rhodium Nanocrystals for Methanol Oxidation Electrocatalysis.
The development of advanced platinum-alternative anode catalysts with high catalytic activity and strong CO poison tolerance is of great significance to break through the technical bottleneck of the direct methanol fuel cell. Herein, we report the spatial construction of a rhodium-decorated three-dimensional macro- and mesoporous architecture built from holey graphene and holey Ti3C2Tx MXene (Rh/HG-HMX) through a combined oxidative-etching and solvothermal coassembly process. Such an exquisite structural design not only fully exposes the internal catalytically active sites as well as improves the mass transfer efficiency of reactants and products, but also affords strong interfacial interactions between metallic Rh and HG-HMX matrix to optimize their electronic structure, thus resulting in significant synergistic catalytic effects. Accordingly, the as-derived Rh/HG-HMX architecture exhibits excellent electrocatalytic methanol oxidation abilities in terms of a large electrochemically active surface area of 171.5 m2·g-1, a high mass activity of 2082.0 mA·mg-1, and dependable long-term durability, far exceeding those of traditional graphene and MXene-supported Rh catalysts as well as commercial Pt/C and Pd/C catalysts.
cell therapies
2021-11-02 | Successful Kidney Transplant From a Brain Stem-Dead Donor Due To Lethal Methanol Poisoning.
Kidney replacement is the best treatment modality for chronic renal failure; however,the greatest obstacle for transplant is the scarce number of donor organs. In the United States and Europe, less than 1% of organs for transplant are provided from patients with lethal poisoning. In this paper, we present a successful kidney transplant from a donor with methanol poisoning. A 38-year-old-man who had methanol poisoning developed brain stem death after unsuccessful treatment and was a candidate to be a kidney donor for transplant to a 27-year-old male patient with chronic renal failure. Three weeks after kidney transplant, the recipient was discharged with good kidney function. We suggest that it may be possible to consider lethal methanol poisoning for kidney donation.
2005-01-04 | Flux Analysis Uncovers Key Role of Functional Redundancy in Formaldehyde Metabolism
Genome-scale analysis of predicted metabolic pathways has revealed the common occurrence of apparent redundancy for specific functional units, or metabolic modules. In many cases, mutation analysis does not resolve function, and instead, direct experimental analysis of metabolic flux under changing conditions is necessary. In order to use genome sequences to build models of cellular function, it is important to define function for such apparently redundant systems. Here we describe direct flux measurements to determine the role of redundancy in three modules involved in formaldehyde assimilation and dissimilation in a bacterium growing on methanol. A combination of deuterium and (14)C labeling was used to measure the flux through each of the branches of metabolism for growth on methanol during transitions into and out of methylotrophy. The cells were found to differentially partition formaldehyde among the three modules depending on the flux of methanol into the cell. A dynamic mathematical model demonstrated that the kinetic constants of the enzymes involved are sufficient to account for this phenomenon. We demonstrate the role of redundancy in formaldehyde metabolism and have uncovered a new paradigm for coping with toxic, high-flux metabolic intermediates: a dynamic, interconnected metabolic loop.
2004-11-01 | Successful bilateral lung transplantation from a methanol-poisoned donor
The shortage of suitable organ donors is an important limiting factor that is making the evaluation of marginal donors necessary and, consequently, allowing expansion of standard donor criteria for organ removal. Lung procurement after methanol poisoning is anecdotal; in fact, there is only one published case in literature and that case showed a successful outcome. In this report, we describe a case of lung donation from a previously healthy individual who died from methanol poisoning. Both lungs were successfully implanted to a 20-year-old man who suffered from cystic fibrosis. This case report is new evidence that lung transplantation from methanol-poisoned donors may be safely performed with a good outcome.
2002-06-01 | Accreditation of skin from a methanol-poisoned victim for banking and grafting
Background. Acute poisoning is a contraindication for organ and tissue donation. In this study the suitability of skin from a methanol-poisoned (MP) donor for future grafting and keratinocytes culturing was investigated. Methods. A patient was admitted with a methanol blood level of 2.7 mg/mL, which became undetectable after 4 days of treatment with 4-methylpyrazole (fomepizole). Upon declared brain death and family consent, organs and skin were harvested. For approving MP skin for grafting, the following parameters were studied: viability and plating efficiency of MP keratinocytes, integrity of MP skin after cryopreservation, and its performance as xenografts on wounds in a pig model. Nonpoisoned (NP) controls included skin of matching age, cryopreservation period, and NP keratinocytes. Results. No significant differences were observed for any parameter between NP and MP samples. Furthermore, in vitro exposure of NP keratinocytes and fibroblasts to <10 mg/mL methanol inhibited their growth by <20%, with an extrapolated LD50 of 100 mg/mL. A parallel exposure to formaldehyde, a spontaneous metabolite of methanol, yielded LD50 of 20 μg/mL and eradication of viability at 300 μg/mL. Conclusions. These results indicate that skin from a carefully monitored MP donor is suitable for banking toward massive burns and skin losses. This methodology may be applied to approve skin harvested from other types of poisoned donors for banking and future grafting.
2001-04-01 | Successful cardiac transplantation with methanol or carbon monoxide-poisoned donors
Background. Patients succumbing to methanol or carbon monoxide poisoning are usually rejected for heart donation. Increasing demand for donors has lead to the expansion of acceptance criteria and increased use of the marginal donor.Methods. We transplanted hearts from donors who had had methanol intoxication in three cases and carbon monoxide exposure in two cases. Standard donor evaluation criteria and transplantation techniques were used.Results. All of the transplants were successful. Three of the recipients required significant inotropic support for a few days postoperatively; however, all of the hearts functioned well over the intermediate and long term. Two recipients (1 from each group) died of complications other than heart failure (1.5 and 2 years postoperatively).Conclusions. Successful heart transplantation can be achieved using the hearts from patients succumbing to methanol or carbon monoxide poisoning. Routine evaluation of cardiac function and myocardial damage is adequate for screening these donors. Hearts from methanol-poisoning victims may require longer inotropic support postoperatively before complete recovery, but can provide excellent long-term function and results.
oligonucleotides
2025-12-29 | Clinical Indicators of Hemodialysis and Mortality in Methanol Poisoning: A Retrospective Analysis.
Methanol poisoning is a severe medical emergency associated with high morbidity and mortality. Methanol poisoning leads to metabolic acidosis, visual disturbances, and central nervous system complications. Early diagnosis and timely treatment, including hemodialysis, are critical in improving outcomes. This study aimed to evaluate the clinical and laboratory predictors of mortality and the need for hemodialysis in methanol poisoning patients. It also sought to establish cutoff values for critical parameters that influence clinical decisions. A single-center retrospective cross-sectional study was conducted on patients over 18 years of age with suspected methanol poisoning between 2010 and 2022. Demographic, clinical, and laboratory data were collected and analyzed. Predictive parameters for mortality and hemodialysis were identified using Receiver Operating Characteristic (ROC) analysis. Sixty-four patients were included, with a mean age of 47.7 years and 92.2% being male. Mortality occurred in 29.7% of patients. ROC analysis identified a serum pH cutoff of ≤7.08 for mortality prediction (AUC: 0.894, P<0.001) and ≤7.315 for predicting the need for hemodialysis (AUC: 0.891, P<0.001). Serum bicarbonate levels were significant predictors, with a cutoff of ≤8.45 for mortality (AUC: 0.820, P<0.001) and ≤15.55 for hemodialysis (AUC: 0.883, P<0.001). Elevated lactate levels (cutoff ≥3.67 mmol/L) and an anion gap ≥27.25 were also strong predictors of mortality. Early recognition of critical parameters such as serum pH, sodium bicarbonate, lactate, and anion gap are essential in managing methanol poisoning.
2022-12-27 | MicroRNA-124 modulates neuroinflammation in acute methanol poisoning rats via targeting Krüppel-like factor-6.
Microglia activation-stimulated neuroinflammation exerts functionally in neurodegenerative diseases like brain injury. Acute methanol poisoning (AMP) is a crucial cause of death and morbidity that possibly leads to neuroinflammation. Studies have manifested that miRNAs can modulate microglia activation to mediate neuroinflammation. Nevertheless, the role of miR-124 in AMP-stimulated neuroinflammation is uncertain. This research was to explore the action of miR-124 in AMP-stimulated neuroinflammation and its molecular mechanism. The study findings indicated that AMP accelerated microglia activation and stimulated inflammation and oxidative stress in brain tissue of rats. MiR-124 expression was lowered in AMP rats, while KLF6 expression was elevated. Elevated miR-124 or repressed KLF6 increased the number of CD206+ cells and decreased the number of CD68+ cells, as well as restrained inflammation and NF-κB phosphorylation and induced superoxide dismutase, Nrf2/HO-1, and M2 polarization. MiR-124 modulated microglia activation via targeting KLF6. AMP repressed neuronal viability and enhanced neuronal apoptosis. Suppression of miR-124 further promoted AMP-induced damage to neurons, while inhibition of KLF6 turned around this phenomenon. Anyway, our study demonstrated that miR-124 accelerates M2 polarization via targeting KLF6 to ameliorate AMP-stimulated neuronal damage.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
2 orphan drug designations for Methanol poisoning, including 1 approved therapy.
2 orphan drug designations for Methanol poisoning, including 1 approved therapy.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
dehydrated alcohol | small molecules | FDA | 2020-07-10 | 2025-10-23 | BE Pharmaceuticals, LLC |
Fomepizole [Mepizol] | small molecules | EMA | 2001-05-30 | — | Idis Limited |
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI’s forecasts to outperform average preclinical success rates. Whether you’re expanding your R&D pipeline, evaluating a partnership, or simply have a question — we’d love to hear from you.