Effects of methazolamide: A Synthesis of Findings from 24 Studies

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Original Abstract of the Article

Major Research Findings

Methazolamide is a carbonic anhydrase inhibitor that has been studied for its potential benefits in various medical conditions. Studies have shown that methazolamide may be effective in treating glaucoma, high altitude illness, intermittent hypoxia, bacterial infections, Alzheimer's disease, and diabetic cardiomyopathy. 15 found that methazolamide selectively inhibits amyloid-β-induced mitochondrial toxicity. 22 demonstrated that methazolamide improves neurological behavior by inhibiting neuron apoptosis in subarachnoid hemorrhage mice. 7 suggested that methazolamide may attenuate the development of diabetic cardiomyopathy by promoting β-catenin degradation in type 1 diabetic mice. Additionally, methazolamide may be a potential therapy for high-altitude illnesses. 10 suggested that methazolamide may be an alternative to acetazolamide for high-altitude illness prophylaxis and treatment due to its higher lipid solubility and fewer side effects. However, methazolamide is known to cause serious skin reactions. reported a case of death due to toxic epidermal necrolysis caused by topical methazolamide ophthalmic solution. 14 suggested that methazolamide-induced Stevens-Johnson syndrome and toxic epidermal necrolysis may be associated with HLA-B*5901 genotype.

Benefits and Risks

Benefit Summary

Methazolamide is a promising drug for the treatment of a variety of medical conditions. It may be effective in treating glaucoma, high altitude illness, intermittent hypoxia, bacterial infections, Alzheimer's disease, and diabetic cardiomyopathy. Particularly, its effects on selectively inhibiting amyloid-β-induced mitochondrial toxicity, improving neurological behavior by inhibiting neuron apoptosis in subarachnoid hemorrhage mice, and promoting β-catenin degradation in type 1 diabetic mice are noteworthy. Methazolamide may also be a potential therapy for high-altitude illnesses due to its higher lipid solubility and fewer side effects compared to acetazolamide.

Risk Summary

Methazolamide is known to cause serious skin reactions. There is a risk of severe side effects such as Stevens-Johnson syndrome and toxic epidermal necrolysis, which can be fatal. These side effects may be associated with HLA-B*5901 genotype.

Comparison Between Studies

Commonalities

Many studies suggest that methazolamide may have promising therapeutic effects on a variety of medical conditions. These studies employ a range of research methods and models to uncover methazolamide's diverse mechanisms of action and its potential therapeutic benefits.

Differences

Studies differ in their findings regarding the efficacy and safety of methazolamide. In particular, there is no consensus among studies on the risk of methazolamide causing serious skin reactions. Factors such as methazolamide dosage, treatment duration, and patient genetic background may contribute to these differences.

Consistency and Contradictions in Findings

Although methazolamide may show promise in treating a variety of conditions, multiple studies have indicated that it can also cause severe skin reactions. Further research is needed to understand the safety and efficacy of methazolamide.

Implications for Everyday Life

Methazolamide should be used cautiously and only under the guidance of a physician, as it can cause serious skin reactions. Genetic testing for HLA-B*5901 genotype may be recommended before administering methazolamide. If using methazolamide, it is important to monitor for side effects such as skin reactions and consult a physician immediately if any abnormalities are observed.

Limitations of Current Research

More research is needed to fully understand the safety and efficacy of methazolamide. In particular, further investigation is needed to determine the risk of methazolamide causing serious skin reactions. Research is also needed to determine how factors such as methazolamide dosage, treatment duration, and patient genetic background impact therapeutic effects and side effects.

Future Research Directions

Large-scale clinical trials are necessary to further evaluate the safety and efficacy of methazolamide. These trials should assess the risk of methazolamide causing severe skin reactions and investigate strategies to mitigate such risks. Additionally, research should explore the impact of factors like methazolamide dosage, treatment duration, and patient genetic background on therapeutic effects and side effects.

Conclusion

Methazolamide is a promising drug for the treatment of a variety of medical conditions. However, it can also cause serious skin reactions. It is important to use methazolamide cautiously and under the guidance of a physician. Further research is needed to evaluate its safety and efficacy, and the results of such studies should guide appropriate methazolamide use.

Literature analysis of 24 papers
Positive Content
19
Neutral Content
1
Negative Content
4
Article Type
2
1
3
3
24
2.

Interventions for acute non-arteritic central retinal artery occlusion.

Author: LinJohn C, SongSophia, NgSueko M, ScottIngrid U, GreenbergPaul B

CRAO treatment

Acute non-arteritic central retinal artery occlusion (CRAO) is a sudden interruption of blood supply to the retina resulting in severe vision loss. While many therapeutic interventions have been proposed, there is no agreed-upon treatment regimen.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

4.

Imatinib and methazolamide ameliorate COVID-19-induced metabolic complications via elevating ACE2 enzymatic activity and inhibiting viral entry.

Author: LiZilun, PengMeixiu, ChenPin, LiuChenshu, HuAo, ZhangYixin, PengJiangyun, LiuJiang, LiYihui, LiWenxue, ZhuWei, GuanDongxian, ZhangYang, ChenHongyin, LiJiuzhou, FanDongxiao, HuangKan, LinFen, ZhangZefeng, GuoZeling, LuoHengli, HeXi, ZhuYuanyuan, LiLinghua, HuangBingding, CaiWeikang, GuLei, LuYutong, DengKai, YanLi, ChenSifan

COVID-19 treatment

This study identified imatinib, methazolamide, and harpagoside as direct activators of the ACE2 pathway, which is impaired in COVID-19 and contributes to metabolic complications. These compounds improved metabolic perturbations in vivo in both insulin-resistant and SARS-CoV-2-infected states. Additionally, they inhibited viral entry by allosterically inhibiting ACE2 binding to the spike protein on SARS-CoV-2. This research suggests that enzymatic activation of ACE2 may represent a novel therapeutic approach for treating metabolic sequelae of COVID-19.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

6.

Cardioprotective effects of N-methylacetazolamide mediated by inhibition of L-type Ca<sup>2+</sup> channel current.

Author: PardoAlejandro Ciocci, Diaz ZegarraLeandro A, González ArbeláezLuisa F, IbáñezAlejandro M, DíazRomina G, AielloErnesto A, MoscaSusana M

Protect myocardium

This study found that N-methylacetazolamide (NMA) protected the myocardium against ischemia-reperfusion injury in isolated rat hearts by decreasing infarct size, improving myocardial function, and attenuating mitochondrial fission. This protective effect was associated with the activation of Akt/PKCε signaling pathways and the decrease of L-type calcium current.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

7.

Methazolamide Attenuates the Development of Diabetic Cardiomyopathy by Promoting β-Catenin Degradation in Type 1 Diabetic Mice.

Author: ChenXiaoqing, LiYilang, YuanXun, YuanWenchang, LiConglin, ZengYue, LianYuling, QiuXiaoxia, QinYuan, ZhangGuiping, LiuXiawen, LuoChengfeng, LuoJian-Dong, HouNing

Cardiomyopathy treatment

Methazolamide (MTZ), a carbonic anhydrase inhibitor, has been shown to have cardioprotective effects in a mouse model of type 1 diabetes mellitus (T1DM). MTZ reduced blood glucose levels, improved glucose tolerance, and ameliorated cardiac dysfunction. These effects are likely mediated by MTZ's ability to decrease β-catenin levels through the promotion of AXIN1-β-catenin interaction and subsequent β-catenin degradation.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

9.

Combined methazolamide and theophylline improves oxygen saturation but not exercise performance or altitude illness in acute hypobaric hypoxia.

Author: SubudhiAndrew W, EveroOghenero, ReitingerJeremy, DavisChristopher, GronewoldJeffrey, NicholsAndrew J, Van-HoutenSonja Jameson, RoachRobert C

Improved oxygen saturation
AMS symptoms
Impaired aerobic performance

This study investigated whether a combination of two drugs could reduce the symptoms of acute mountain sickness (AMS) and improve aerobic performance at high altitude. The study found that the combination of drugs did not reduce AMS symptoms and impaired aerobic performance.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.

Language : English

10.

Methazolamide in high-altitude illnesses.

Author: LuHui, ZhangHuaqun, JiangYuanying

High-altitude illness prevention
High-altitude illness treatment
Reduced fatigue

Methazolamide, a carbonic anhydrase inhibitor, has higher lipid solubility and fewer side effects compared to acetazolamide. It can increase systemic metabolic acidosis and improve ventilation and oxygenation level. This review discusses the advantages of methazolamide over acetazolamide for high-altitude illnesses prophylaxis and treatment.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

11.

Influence of methazolamide on the human control of breathing: A comparison to acetazolamide.

Author: TeppemaLuc J, BouletLindsey M, HackettHeather K, DominelliPaolo B, CheyneWilliam S, DominelliGiulio S, SwensonErik R, FosterGlen E

Reduced hypoxic pulmonary vasoconstriction
Metabolic acidosis

This study investigates the effects of methazolamide, a carbonic anhydrase inhibitor, on respiratory control in humans. It finds that methazolamide, similar to acetazolamide, causes a metabolic acidosis and shifts the ventilatory CO2 response curve leftwards without impairing oxygen sensitivity. It suggests that methazolamide could be a valuable alternative to acetazolamide in treating certain respiratory conditions.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

13.

Comprehensive assessment of T cell receptor β repertoire in Stevens-Johnson syndrome/toxic epidermal necrolysis patients using high-throughput sequencing.

Author: XiongHao, WangLanting, JiangMenglin, ChenShengan, YangFanping, ZhuHuizhong, ZhuQinyuan, TangChenling, QinShengying, XingQinghe, LuoXiaoqun

SJS/TEN treatment

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe skin reactions to medications. This study examined the T cell receptor (TCR) repertoire in 17 patients with SJS/TEN associated with three different drugs. The findings revealed that SJS/TEN patients had more highly expanded TCR clones and less TCR repertoire diversity. The study also identified similar predominant clonotypes and shared TCR subtypes among patients with the same causative drug. These findings provide insights into the role of T cells in SJS/TEN and potential therapeutic targets.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

14.

Association between HLA-B*5901 and methazolamide-induced Stevens-Johnson syndrome/toxic epidermal necrolysis: a systematic review and meta-analysis.

Author: TangamornsuksanWimonchat, LohitnavyManupat

Genetic screening
Hypersensitivity
SJS/TEN

Methazolamide can cause Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), which are serious skin reactions. Genetic testing for HLA-B*5901 and HLA-B*5901-Cw*0102 haplotype before using methazolamide is recommended for Asian populations, as these genes are associated with an increased risk of SJS/TEN.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

15.

Carbonic anhydrase inhibition selectively prevents amyloid β neurovascular mitochondrial toxicity.

Author: SolesioMaría E, PeixotoPablo M, DebureLudovic, MadambaStephen M, de LeonMony J, WisniewskiThomas, PavlovEvgeny V, FossatiSilvia

Alzheimer's disease prevention

Carbonic anhydrase inhibitors (CAIs) may be a new treatment for Alzheimer's disease (AD). The CAIs methazolamide (MTZ) and acetazolamide (ATZ) were shown to protect neuronal and cerebral vascular cells from amyloid β (Aβ)-induced mitochondrial dysfunction. Both drugs prevented mitochondrial membrane depolarization and H2O2 generation, without affecting intracellular pH or ATP production. Importantly, the drugs did not primarily affect calcium homeostasis.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

16.

Effect of acetazolamide and methazolamide on diaphragm and dorsiflexor fatigue: a randomized controlled trial.

Author: DominelliPaolo B, McNeilChris J, VermeulenTyler D, StucklessTroy J R, BrownCourtney V, DominelliGiulio S, SwensonErik R, TeppemaLucas J, FosterGlen E

Muscle fatigue

This study compared the effects of acetazolamide and methazolamide on diaphragm and dorsiflexor fatigue in healthy men. Methazolamide led to less neuromuscular fatigue than acetazolamide, suggesting a potential benefit for clinical use or in the prophylaxis of acute mountain sickness.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

17.

Therapeutic Efficacy of Methazolamide Against Intermittent Hypoxia-Induced Excessive Erythrocytosis in Rats.

Author: ZhangZhiqing, XiaoZhonghai, DengBingnan, LiuXiaohua, LiuWei, NieHongjing, LiXi, ChenZhaoli, YangDanfeng, DuanRuifeng

Erythrocytosis treatment
Lipid metabolism improvement
Oxygen transport improvement
Hypoxia

Methazolamide, a carbonic anhydrase inhibitor, showed dose-dependent efficacy in treating excessive erythrocytosis induced by long-term hypoxia in rats. Methazolamide reduced hemoglobin concentration, hematocrit, and blood viscosity, and it also had beneficial effects on oxygen transport and lipid metabolism.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

18.

Treatment of cystoid macular edema secondary to retinitis pigmentosa: a systematic review.

Author: BakthavatchalamMalini, LaiFrank H P, RongShi Song, NgDanny S, BrelenMarten E

CME treatment
Oral acetazolamide
CME rebound

Oral carbonic anhydrase inhibitors are effective first-line treatments for cystoid macular edema (CME) secondary to retinitis pigmentosa. Oral acetazolamide is the most effective treatment, but topical dorzolamide is a suitable alternative for patients who cannot tolerate oral acetazolamide.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

22.

Methazolamide improves neurological behavior by inhibition of neuron apoptosis in subarachnoid hemorrhage mice.

Author: LiMingchang, WangWei, MaiHaojian, ZhangXinmu, WangJian, GaoYufeng, WangYuefei, DengGang, GaoLing, ZhouShuanhu, ChenQianxue, WangXin

Cerebral edema relief
Cognitive function improvement
Neurological recovery

Methazolamide, a carbonic anhydrase inhibitor, has neuroprotective effects in a subarachnoid hemorrhage (SAH) animal model and in blood-induced primary cortical neuron (PCNs) cellular model of SAH. It accelerates recovery of neurological damage, relieves cerebral edema, and improves cognitive function, but does not protect against mortality, cerebral blood flow fluctuations, SAH grade, or cerebral vasospasm.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

24.

Berbamine inhibited the growth of prostate cancer cells in vivo and in vitro via triggering intrinsic pathway of apoptosis.

Author: ZhaoY, LvJ J, ChenJ, JinX B, WangM W, SuZ H, WangL Y, ZhangH Y

PCa treatment

Berbamine (BBM) effectively inhibited prostate cancer (PCa) cell growth in vitro and in vivo by inducing apoptosis through the mitochondrial pathway. BBM activated caspase-3, leading to cell death.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

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