It is a precursor of piperidine, which has been linked with some functional stages of the CNS. Cadaverine is the source of much of the piperidine excreted in the urine.
Cadaverine ... a relatively nontoxic ptomaine, C5H14N2, formed by decarboxylation of lysine; it is sometimes one of the products of Vibrio proteus and of V. cholerae, and occasionally found in the urine in cystinuria, where it causes an unpleasant odor.
IDENTIFICATION AND USE: Cadaverine is a syrupy, colorless liquid with a distinctive odor of urine and semen. It is soluble in water, ethanol; slightly soluble in ethyl ether, and miscible in water. It is used in the production of high polymers, as a chemical intermediate, and in biological research. HUMAN EXPOSURE AND TOXICITY: It is a foul-smelling diamine formed by bacterial decarboxylation of lysine. It is poisonous and irritating to the skin. Harmful if ingested, inhaled, or absorbed through the skin. It can cause burns and is very destructive of mucous membranes. Occupational exposure to cadaverine may occur through inhalation and dermal contact with this compound at workplaces where it is produced or used. Monitoring data indicate that the general population may be exposed to cadaverine by ingestion of certain meats. ANIMAL STUDIES: In In rats, cadaverine had a low oral toxicity. Cadaverine caused a dose-related decrease in blood pressure after intravenous administration in rats. The subacute toxicity of this chemical was examined in rats. Cadaverine was administered in the diet to groups of 10 male and 10 female rats. Adverse effects were observed in the high dose group and decreased body weights associated with diminished food intake were observed. Slight increases in packed cell volume, hemoglobin concentration, and thrombocytes occurred with chemical exposure.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
副作用
Dermatotoxin - 皮肤烧伤。
Dermatotoxin - Skin burns.
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
Histamine poisoning can result from the ingestion of food containing unusually high levels of histamine. ... Histamine poisoning is characterized by a short incubation period, a short duration, and symptoms resembling those associated with allergic reactions. The evidence supporting the role of histamine as the causative agent is compelling. ... Histamine ingested with spoiled fish appears to be much more toxic than histamine ingested in an aqueous solution. The presence of potentiators of histamine toxicity in the spoiled fish may account for this difference in toxicity. Several potentiators including other putrefactive amines such as putrescine and cadaverine have been identified. Pharmacologic potentiators may also exist; aminoguanidine and isoniazid are examples. The mechanism of action of these potentiators appears to be the inhibition of intestinal histamine-metabolizing enzymes. This enzyme inhibition causes a decrease in histamine detoxification in the intestinal mucosa and results in increased intestinal uptake and urinary excretion of unmetabolized histamine.
/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/
The urinary excretion of histamine, methylhistamine, putrescine, cadaverine, spermidine and spermine was examined before, during and after pregnancy in rats. During the last third of undisturbed pregnancy a distinct and steep rise occurred in the excretion of all amines studied except spermine. The peak values were found a few days before the birth of the young. In spermidine excretion a second peak was observed one or two days after delivery. Before and during the first 2 weeks of gestation on a molar basis putrescine excretion was the greatest one. During the last trimester histamine was excreted in the largest amount. Under the influence of the diamine oxidase inhibitor aminoguanidine the general pattern of excretion of diamines and polyamines in pregnant rats remained essentially unchanged but the total amount excreted increased. Most conspicuous was the great elevation of urinary contents of putrescine and cadaverine.
Cadaverine has been shown to be present in the central nervous system (CNS) ... Its concentration in the whole brain varies during behavioral sleep in mammals and during hibernation in molluscs. ... Cadaverine has been considered a non-metabolite of the brain, and its presence in the body was believed to be due almost entirely to bacterial decarboxylation of lysine in the intestine. In slices of mouse brain, exogenous cadaverine accumulates against a concentration gradient and can reach a concentration ten times greater in the tissue than in the surrounding medium. The question has been therefore: does the cadaverine in the brain originate from an exogenous source; is it formed and resorbed in the intestine? Assaying cadaverine in axenic mice, /it has been/ found that this is not the case, and that there is an endogenous source of cadaverine in the mouse.
Synthesis and Biological Evaluation of the First Dual Tyrosyl-DNA Phosphodiesterase I (Tdp1)–Topoisomerase I (Top1) Inhibitors
作者：Trung Xuan Nguyen、Andrew Morrell、Martin Conda-Sheridan、Christophe Marchand、Keli Agama、Alun Bermingam、Andrew G. Stephen、Adel Chergui、Alena Naumova、Robert Fisher、Barry R. O’Keefe、Yves Pommier、Mark Cushman
DOI：10.1021/jm300335n
日期：2012.5.10
Substances with dualtyrosyl-DNAphosphodiesterase I–topoisomerase I inhibitory activity in one low molecular weight compound would constitute a unique class of anticancer agents that could potentially have significant advantages over drugs that work against the individual enzymes. The present study demonstrates the successful synthesis and evaluation of the firstdual Top1–Tdp1 inhibitors, which are based
[EN] MACROCYCLIC COMPOUNDS FOR MODULATING IL-17<br/>[FR] COMPOSÉS MACROCYCLIQUES POUR UNE MODULATION D'IL-17
申请人：ENSEMBLE THERAPEUTICS CORP
公开号：WO2013116682A1
公开（公告）日：2013-08-08
The invention relates generally to macrocyclic compounds of formula I and their therapeutic use. More particularly, the invention relates to macrocyclic compounds that modulate the activity of IL-17 and/or are useful in the treatment of medical conditions, such as inflammatory diseases and other IL-17-associated disorders.
Synthesis and Aggregation Properties of Two- and Three-Armed Nitrogen-Rich Chelate Ligands: Novel Bis(N-acylamidines), Tris(N-acylamidines) and Bis(triazapentadienes) with Flexible or Rigid Spacers
and three-armed ligands, like bis(N-acylamidines) 7 and 9, tris(N-acylamidines) 8 and bis(1,3,5-triazapenta-1,3-dienes) 10 with different spacers between the ligand moieties, have been easily prepared in moderate-to-good yields starting from diamines, triamines or dicarboxylic acid derivatives. Thus, the reaction of diamines and triamines with N-acylimidates 3 led to bis(N-acylamidines) 7 and tris(N-acylamidines)
The blood-brain barrier (BBB) is a highly selective membranous barrier regulating the transport of substances in blood into the brain parenchyma. At present, delivery of biologically active peptides or peptide drugs into the brain is quite an important subject from the standpoint of chemotherapy for brain diseases. H–MeTyr–Arg–MeArg–d-Leu–NH(CH2)8NH2 termed 001-C8 was first synthesized to elucidate the structural specificity of peptides for passing through the BBB. The Nα-methylamino acid and d-amino acid residues were appropriately situated in this peptide to protect against the digestion by peptidase. Furthermore, a number of basic peptides were prepared as 001-C8 analogs for studying the relationship between structure and BBB permeability of peptides.
Iodoaminopotentidine and related compounds: a new class of ligands with high affinity and selectivity for the histamine H2 receptor
作者：Juergen Hirschfeld、Armin Buschauer、Sigurd Elz、Walter Schunack、Martial Ruat、Elisabeth Traiffort、Jean Charles Schwartz
DOI：10.1021/jm00090a013
日期：1992.6
The synthesis and biologicalevaluation of a new class of histamine H2 antagonists with N-cyano-N'-[omega-[3-(1-piperidinylmethyl)phenoxy] alkyl]guanidine partial structure are described as part of an extensive research program to find model compounds for the development of new radioligands with high H2 affinity and specific activity. High receptor affinity is achieved by an additional (substituted)
