Following distribution into tissues, rapidly reduced to leukomethylene blue (leucomethylthioninium chloride). Metabolism to leucomethylene blue may be less efficient in neonates than in older individuals.
Methylene blue can be reduced to a colorless form, leukomethylene blue; together, these compounds form a reversible oxidation-reduction system. In low concentrations, methylene blue accelerates conversion of methemoglobin to hemoglobin. In patients with methemoglobinemia, methylene blue is reduced to leukomethylene blue by methemoglobin reductases in erythrocytes; leukomethylene blue then reduces methemoglobin to hemoglobin. In high concentrations, methylene blue oxidizes the ferrous iron of reduced hemoglobin to the ferric state, thereby changing hemoglobin to methemoglobin.
来源:Hazardous Substances Data Bank (HSDB)
代谢
随后分布到组织中，美蓝迅速还原为白乐美蓝（白乐甲硫氮氯）。与年长者相比，新生儿的代谢效率可能较低。
Following distribution into tissues, methylene blue is rapidly reduced to leukomethylene blue (leucomethylthioninium chloride). Metabolism to leucomethylene blue may be less efficient in neonates than in older individuals.
IDENTIFICATION AND USE: Methylene blue is a solid. Water solutions are deep blue. It is used as a stain in bacteriology, as mixed indicator, a dye, a redox colorimetric agent, and a targeting agent for melanoma. It is also used as a medication to treat drug-induced methemoglobinemia. HUMAN STUDIES: Methemoglobinemia is usually treated with methylene blue. However, in patients with glucose-6-phosphate dehydrogenase deficiency, methylene blue can induce methemoglobinemia. Preclinical studies have shown that low-dose methylene blue increases mitochondrial cytochrome oxidase activity in the brain and improves memory retention after learning tasks, including fear extinction. The intracameral use of 1% methylene blue has a cytotoxic effect on the corneal endothelium and iris epithelium. Several cases of suspected serotonin syndrome have been reported in patients who received methylene blue in combination with serotonin active agents. Allergic hypersensitivity reaction to methylene blue-treated plasma transfusion has also been reported. A preterm infant had methemoglobulinemia and hemolytic anemia after enteral administration of methylene blue. There is epidemiologic evidence that methylene blue is a teratogen, and the drug can cause fetal harm if administered during pregnancy. Use of methylene blue in amniocentesis has been associated with atresia of the ileum and jejunum, ileal occlusion, and other adverse effects in neonates. Use of methylene blue during pregnancy has resulted in hemolytic anemia, hyperbilirubinemia, methemoglobinemia, respiratory distress, skin staining, and phototoxicity in neonates. ANIMAL STUDIES: Methylene blue treatment resulted in methemoglobin formation and oxidative damage to red blood cells, leading to a regenerative anemia and a variety of tissue and biochemical changes secondary to erythrocyte injury. An early change was a dose-related increase in methemoglobin, where the response of rats and mice was similar in magnitude. Mice appeared to be more sensitive than rats to the formation of Heinz bodies and the development of anemia that was characterized by a decrease in hemoglobin, hematocrit, and erythrocyte count. Splenomegaly was apparent in all treated mice and in the 100 mg/kg (males only) and 200 mg/kg rats at necropsy. Methylene blue was embryotoxic in the rat. Methylene blue caused the mice to deliver before gestation day 18 (term gestation). This response was observed in 45%, 50% and 83% of animals receiving methylene blue at 50, 60 or 85 mg/kg, respectively. Under cell-free conditions methylene blue induced DNA damage. It is characterized by a high number of base modifications sensitive to the repair endonuclease FPG protein (formamidopyrimidine-DNA glycosylase). Methylene blue was mutagenic in cultured mammalian cells. In contrast, results from the mouse micronucleus assay suggest that the genotoxicity is not expressed in vivo. The greatest concerns with methylene blue therapy in veterinary use are the development of Heinz body anemia or other red cell morphological changes, methemoglobinemia, and decreased red cell life spans. Cats tent to be very sensitive to these effects and some consider it contraindicated in feline patients, but dogs and horses can also develop hematologic adverse effects at relatively low dosages. ECOTOXICITY STUDIES: Methylene blue had a teratogenic effect in angelfish.
Evaluation: No data were available to the Working Group for humans. There is limited evidence for the carcinogenicity of methylene blue in experimental animals. Overall evaluation: Methylene blue is not classifiable as to its carcinogenicity in humans (Group 3).
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌物分类
国际癌症研究机构致癌物：亚甲基蓝
IARC Carcinogenic Agent:Methylene blue
来源:International Agency for Research on Cancer (IARC)
毒理性
致癌物分类
国际癌症研究机构（IARC）致癌物分类：第3组：无法归类其对人类致癌性
IARC Carcinogenic Classes:Group 3: Not classifiable as to its carcinogenicity to humans
来源:International Agency for Research on Cancer (IARC)
毒理性
致癌物分类
国际癌症研究机构专著：第108卷：（2016年）一些药物和草药产品
IARC Monographs:Volume 108: (2016) Some Drugs and Herbal Products
来源:International Agency for Research on Cancer (IARC)
吸收、分配和排泄
消除途径
分泌在尿液和胆汁中。口服剂量的约75%通过尿液排出，主要是以稳定的无色 leukomethylene blue 形式。
Excreted in urine and bile. About 75% of an oral dose excreted in urine, primarily as stabilized colorless leukomethylene blue.
... The concentration of methylene blue in whole blood was measured using high-performance liquid chromatography in seven volunteers after IV and oral administration of 100 mg methylene blue with and without mesna. The distribution of methylene blue in different tissues was measured in rats after intraduodenal and IV application. The time course of methylene blue in whole blood after IV administration showed a multiphasic time course with an estimated terminal half-life of 5.25 hr. Following oral administration, the area under the concentration-time curve was much lower (9 nmol/min/mL vs 137 nmol/min/mL). Co-administration of mesna, which could influence distribution by ion-pairing, did not alter the pharmacokinetics. The urinary excretion of methylene blue and its leukoform was only moderately higher after IV administration (18% vs 28% dose). Intraduodenal administration to rats resulted in higher concentrations in intestinal wall and liver but lower concentrations in whole blood and brain than IV methylene blue. Differences in organ distribution of methylene blue are mainly responsible for the different pharmacokinetics after oral and IV administration. ...
Methylene blue is well absorbed from the GI tract, and peak plasma concentrations occur approximately 1-2 hours after an oral dose. ... Following distribution into tissues, methylene blue is rapidly reduced to leukomethylene blue (leucomethylthioninium chloride). Metabolism to leucomethylene blue may be less efficient in neonates than in older individuals. Methylene blue is excreted in urine and bile. About 75% of an oral dose of methylene blue is excreted in urine, mostly as stabilized colorless leukomethylene blue. On exposure to air, the urine turns green or blue, due to the presence of the oxidation product methylene azure (methylene blue sulfone). Some unchanged drug is also excreted in urine.
Provided are novel compounds that inhibit LRRK2 kinase activity, processes for their preparation, compositions containing them and their use in the treatment of or prevention of diseases associated with or characterized by LRRK2 kinase activity, for example Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis (ALS).
[EN] PHENOTHIAZINE DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS DE PHÉNOTHIAZINE ET LEURS UTILISATIONS
申请人：CAMP4 THERAPEUTICS CORP
公开号：WO2019195789A1
公开（公告）日：2019-10-10
The present invention provides phenothiazine compounds, processes for their preparation, pharmaceutical compositions comprising the compounds, and the use of the compounds or the compositions in the treatment of various diseases or conditions, for example ribosomal disorders and ribosomopathies, e.g. Diamond Blackfan anemia (DBA).
Benzene Sulfonamide Thiazole and Oxazole Compounds
申请人：Adams Jerry Leroy
公开号：US20090298815A1
公开（公告）日：2009-12-03
The present invention provides thiazole sulfonamide and oxazole sulfonamide compounds, compositions containing the same, as well as processes for the preparation and methods for their use as pharmaceutical agents.
The present invention provides novel conformationally-defined macrocyclic compounds that have been demonstrated to be selective modulators of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R1a and subtypes, isoforms and variants thereof). Methods of synthesizing the novel compounds are also described herein. These compounds are useful as agonists of the ghrelin receptor and as medicaments for treatment and prevention of a range of medical conditions including, but not limited to, metabolic and/or endocrine disorders, gastrointestinal disorders, cardiovascular disorders, obesity and obesity-associated disorders, central nervous system disorders, genetic disorders, hyperproliferative disorders and inflammatory disorders.
COMPOSITIONS AND METHODS FOR DETECTING NERVE AGENTS
申请人：Corcoran Robert C.
公开号：US20100130757A1
公开（公告）日：2010-05-27
The present invention provides methods and compositions for detecting, identifying and measuring the abundance of chemical nerve agents. Methods and compositions of the present invention are capable of providing selective detection of phosphorous based nerve agents, such as nerve agents that are esters of methyl phosphonic acid derivatives incorporating a moderately good leaving group at the phosphorus. Selectivity in the present invention is provided by a sensor composition having an alpha (α) effect nucleophile group that undergoes specific nucleophilic substitution and rearrangement reactions with phosphorus based nerve agents having a tetrahederal phosphorous bound to oxygen. The present invention includes embodiments employing a sensor composition further comprising a reporter group covalently linked to the alpha effect nucleophile group allowing rapid optical readout of nerve agent detection events, including direct visual readout and optical readout via spectroscopic analysis.
