Lead and cyanide are absorbed following inhalation, oral, and dermal exposure. Lead is then distributed mainly to the bones and red blood cells. In the blood lead may be found bound to serum albumin or the metal-binding protein metallothionein. Organic lead is metabolized by cytochrome P-450 enzymes, whereas inorganic lead forms complexes with delta-aminolevulinic acid dehydratase. Lead is excreted mainly in the urine and faeces. Organic nitriles are converted into cyanide ions through the action of cytochrome P450 enzymes in the liver. Cyanide is rapidly absorbed and distributed throughout the body. Cyanide is mainly metabolized into thiocyanate by either rhodanese or 3-mercaptopyruvate sulfur transferase. Cyanide metabolites are excreted in the urine. (L96, L136)
Lead mimics other biologically important metals, such as zinc, calcium, and iron, competing as cofactors for many of their respective enzymatic reactions. For example, lead has been shown to competitively inhibit calcium's binding of calmodulin, interferring with neurotransmitter release. It exhibits similar competitive inhibition at the NMDA receptor and protein kinase C, which impairs brain microvascular formation and function, as well as alters the blood-brain barrier. Lead also affects the nervous system by impairing regulation of dopamine synthesis and blocking evoked release of acetylcholine. However, it's main mechanism of action occurs by inhibiting delta-aminolevulinic acid dehydratase, an enzyme vital in the biosynthesis of heme, which is a necesssary cofactor of hemoglobin. Organic nitriles decompose into cyanide ions both in vivo and in vitro. Consequently the primary mechanism of toxicity for organic nitriles is their production of toxic cyanide ions or hydrogen cyanide. Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected. Cyanide is also known produce some of its toxic effects by binding to catalase, glutathione peroxidase, methemoglobin, hydroxocobalamin, phosphatase, tyrosinase, ascorbic acid oxidase, xanthine oxidase, succinic dehydrogenase, and Cu/Zn superoxide dismutase. Cyanide binds to the ferric ion of methemoglobin to form inactive cyanmethemoglobin. (T4, A20, A22, L97, L136)
来源:Toxin and Toxin Target Database (T3DB)
毒理性
致癌性证据
A3；已确认对动物有致癌性，但对人类的相关性未知。/铅和无机化合物，如铅/
A3; Confirmed animal carcinogen with unknown relevance to humans. /Lead and inorganic compounds, as Pb/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
铅、铅化合物：合理预期为人类致癌物
Lead, lead compounds: Reasonably anticipated to be a human carcinogen
Organic lead compounds are not classifiable as to their carcinogenicity to humans (Group 3). To the extent that organic lead compounds are metabolized in part to ionic lead, they are expected to exert the toxicities associated with inorganic lead (Group 2A, probably carcinogenic to humans). (L135)
Lead is a neurotoxin and has been known to cause brain damage and reduced cognitive capacity, especially in children. Lead exposure can result in nephropathy, as well as blood disorders such as high blood pressure and anemia. Lead also exhibits reproductive toxicity and can results in miscarriages and reduced sperm production. Exposure to high levels of cyanide for a short time harms the brain and heart and can even cause coma, seizures, apnea, cardiac arrest and death. Chronic inhalation of cyanide causes breathing difficulties, chest pain, vomiting, blood changes, headaches, and enlargement of the thyroid gland. Skin contact with cyanide salts can irritate and produce sores. (L21, L96, L97)
Phenylsulfonyl nitromethanes as aldose reductase inhibitors
申请人：Imperial Chemical Industries PLC
公开号：US05153227A1
公开（公告）日：1992-10-06
The invention concerns novel pharmaceutical compositions for use in the treatment of certain complications of diabetes and galactosemia and which contain a nitromethane derivative (or its non-toxic salt) as active ingredient. The nitromethane derivatives are inhibitors of the enzyme aldose reductase. Many of the inhibitors are novel and are provided, together with processes for their manufacture and use, as further features of the invention.
Pyridyl and pyridazinyl substituted thyronine compounds
申请人：Smith Kline & French Laboratories Limited
公开号：US04910305A1
公开（公告）日：1990-03-20
This invention relates to chemical compounds which have selective thyromimetic activity. A compound of this invention is 3,5-dibromo-3'-[6-oxo-3(1H)-pyridazinylmethyl]-thyronine.
5-Aryl-1-(2-oxazolin-2-yl)-1H-1,4-benzodiazepines and related compounds
申请人：G. D. Searle & Co.
公开号：US04208327A1
公开（公告）日：1980-06-17
5-Aryl-1-(2-oxazolin-2-yl)-1H-1,4-benzodiazepines and related compounds having the formula ##STR1## wherein A is methylene or carbonyl; Z is oxygen, imino or thio; R.sup.1, R.sup.2, and R.sup.3 independently are hydrogen, halogen, trifluoromethyl or nitro; R.sup.4 is hydrogen or hydroxy; and n is positive integer from 1 to 3 inclusive are disclosed. These compounds are useful because of their central nervous system activity.
Pyridyl and pyridazinyl substituted thyronine compounds having selective
申请人：Smith Kline & French Laboratories Ltd.
公开号：US04766121A1
公开（公告）日：1988-08-23
This invention relates to chemical compounds which have selective thyromimetic activity. A compound of this invention is 3,5-dibromo-3'-[6-oxo-3(1H)-pyridazinylmethyl]-thyronine.
The present invention relates to compounds that modulate neurotransmission by promoting the release of neurotransmitters such as acetylcholine, dopamine and norepinephrine. More particularly, the present invention relates to thio-bridged aryl compounds that are capable of modulating acetylcholine receptors and pharmaceutical compositions comprising such compounds. The compounds disclosed are useful for the treatment of dysfunctions of the central and autonomic nervous systems.
