SEARCH · Search PubMed

Results for “Dimethylamines”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 739 records · Page 41Linked to original sources

PubMed1997

[A research on the determination of trace secondary amines by reversed-phase high performance liquid chromatography with electrochemical detection].

A new sensitive method for determination of ultratrace secondary amines has been described. It is the first time to use dansyl chloride as electrochemical derivatization reagent for secondary amines. The optimum experimental conditions have been established. At first, trace secondary amines were derivatised with dansyl chloride at 40 degrees C for 30 minutes, then the mixture was injected and separated on a Perkin-Elmer/HS-3 C18 (83 mm x 4.6 mm i.d. 3 microm) column with methanol aqueous solution (70/30, pH 3.3) which contained 20 mmol/L potassium biphthalate buffer as mobile phase and detected with electrochemical detection at E = +1.1 V (Ag/AgCl). The calibration curves were linear in the range of 0.225-54 pg for dimethylamine; 1.1-264 pg for diethylamine, 0.43-102 pg for piperidine. The detection limits were 0.024, 0.60, 0.090 pg respectively and the coefficients of variation were less than 3.5% (n = 7).

Amines↗

PubMed2005

Adsorption of catechol from aqueous solution by aminated hypercrosslinked polymers.

Adsorption of catechol from aqueous solution with the hypercrosslinked polymeric adsorbent NDA-100 and its derivatives AH-1, AH-2 and AH-3 aminated by dimethylamine, the commercial resin Amberlite XAD-4 and weakly basic anion exchanger resin D301 was compared. It was found that the aminated hypercrosslinked resins had the highest adsorption capacities among the tested polymers. The empirical Freundlich equation was successfully employed to describe the adsorption process. Specific surface area and micropore structure of the adsorbent, in company with tertiary amino groups on matrix affected the adsorption performance towards catechol. In addition, thermodynamic study was carried out to interpret the adsorption mechanism. Kinetic study testified that the tertiary amino groups on the polymer matrix could decrease the adsorption rate and increase the adsorption apparent activation energy.

Adsorption↗

PubMed2005

Sibutramine therapy in obese women--effects on plasma neuropeptide Y (NPY), insulin, leptin and beta-endorphin concentrations.

OBJECTIVE: Some neuropeptides and monoaminergic neurotransmitters may affect hypothalamic feeding centres, sympathetic activity and thermogenesis. Sibutramine (BTS54524; N-[1-[1(4-chloro phenyl) cyclobutyl]-3methyl N,N-dimethylamine hydrochloride monohydrate) is a new 5-HT serotonin and noradrenaline reuptake inhibitor (SNRI), antiobesity drug. The aim of this study was to evaluate the effects of the sibutramine therapy on plasma neuropeptide Y (NPY), insulin, leptin and beta-endorphin concentrations in obese patients. METHODS: Sibutramine, serotonin and noradrenaline reuptake antiobesity drug was administered for 6 months in a dose of 10 mg daily in 60 obese women (BMI 30-40 kg/m2) (mean 34 kg/m2). Plasma NPY, leptin, beta-endorphin and insulin concentrations were measured with RIA methods using commercial kits (Peninsula Lab, Linco, Peninsula Lab, Swierk respectively). The above neuropeptides levels were evaluated before and after the 6 month sibutramine therapy in 60 obese women as well as in 30 obese women on low caloric diet and in 30 of the control group. RESULTS: In 85% obese patients a decrease of body weight was found after 6 month therapy with sibutramine. A decrease in total cholesterol, LDL and triglycerides and an increase in HDL were observed after the sibutramine treatment. We have demonstrated that the sibutramine therapy leads to the decrease of plasma NPY, beta-endorphin, insulin and leptin concentrations in obese patients. After low diet therapy we have observed a decrease in plasma leptin levels, however we did not find significant changes in plasma leptin, NPY, beta-endorphin and insulin concentrations. CONCLUSIONS: We suggest that the effects on the disturbed activity of NPY, beta-endorphin, insulin and leptin may be involved in the mechanism of sibutramine action.

Adolescent↗

PubMed2005

Synthesis of 2-azabicyclo[3.2.2]nonanes from bicyclo[2.2.2]octan-2-ones and their activities against Trypanosoma brucei rhodesiense and Plasmodium falciparum K1.

PURPOSE: New 2-azabicyclo[3.2.2]nonanes were prepared from antiprotozoal bicyclo[2.2.2]octan-2-ones to investigate the influence of the replacement of the rigid bicyclo-octane structure by the more flexible bicyclo-nonane system on the antiplasmodial and antitrypanosomal activity. METHODS: The 2-azabicyclo[3.2.2]nonanes were synthesized via a one-step procedure from bicyclo[2.2.2]octan-2-ones and tested for their activities against Trypanosoma b. rhodesiense and Plasmodium falciparum K1 (resistant to chloroquine and pyrimethamine) using in vitro microplate assays. RESULTS: 2-azabicyclo[3.2.2]non-5-ylamines exhibit higher antiprotozoal activities than 4-aminobicyclo[2.2.2]octanes, 4-aminobicycl [2.2.2]octan-2-ones and 4-amino-2-azabicyclo[3.2.2]nonan-3-ones. (7, 8-Diphenyl-2-azabicyclo[3.2.2]non-5-yl)-dimethylamine shows enhanced anti-trypanosomal (IC50 = 0.60 microM) and remarkable antiplasmodial (IC50 = 0.28 microM) activity. However, the in vivo activity of this compound against Plasmodium berghei in mice is moderate. CONCLUSIONS: Due to their promising in vitro antiprotozoal activity and their low cytotoxicity, 2-azabicyclo[3.2.2]nonanes should serve as lead compounds for further modifications.

Animals↗

PubMedDate not supplied

Asymmetric dimethylarginine (ADMA) as a target for pharmacotherapy.

Asymmetric dimethylarginine (ADMA) is synthesized during the methylation of protein arginine residues by protein arginine methyltransferases (PRMT) and is released during proteolysis. ADMA is a competitive inhibitor of nitric oxide synthase and may decrease NO availability. ADMA is eliminated by renal excretion or is metabolized by dimethylarginine dimethylaminohydrolase (DDAH) to citruline and dimethylamine. Two other endogenous methylarginines are also synthesized by PRMT: N-monomethyl-L-arginine (L-NMMA) and symmetric dimethylarginine (SDMA). L-NMMA inhibits NO synthase but its concentrations in circulation are much lower than ADMA whereas SDMA is inactive. Plasma concentration of ADMA is markedly increased in patients with chronic renal failure and moderately increased in patients with many other diseases including hyperlipidemia, diabetes mellitus, arterial hypertension, hyperhomocysteinemia and heart failure. The increased concentration of ADMA is positively correlated with markers of atherosclerosis, such as carotid artery intima-media thickness and has a predictive value for acute cardiovascular events in prospective studies. Angiotensin-converting enzyme inhibitors, angiotensin AT1 receptor antagonists, vitamin E and, according to some studies, estrogens used in hormonal replacement therapy reduce plasma ADMA concentration, which may contribute to their beneficial effect on NO synthesis and endothelial function. However, in some states associated with excess of NO, such as septic shock or excitotoxic neuronal injury ADMA may be protective by limiting toxic effect of high concentrations of NO. This article reviews the effect of pharmacotherapy on ADMA metabolism and its possible clinical implications.

Animals↗

PubMed1991

2,4-D toxicosis.III: An attempt to produce 2,4-D toxicosis in dogs on treated grass plots.

Eighteen English pointer dogs were randomly assigned to 3 outdoor grass-plot enclosures (6/enclosure) uniformly sprayed once with either the 2,4-dichlorophenoxyacetic acid (2,4-D) dimethylamine formulation (DMA-4) at the maximum recommended application rate, DMA-4 at 4 times the maximum recommended application rate, or the DMA-4 vehicle alone at 4 times the maximum recommended application rate. A heavy rain shower occurred 24 h after application. The dogs were observed for clinical signs and evaluated using an electroencephalograph, electrocardiograph (lead I), and electromyograph prior to exposure, and either 1 or 7 d after continuous exposure. Clinical examination, hematologic and serum biochemical data were obtained, and serum, urine and kidney 2,4-D were quantified. Half of the dogs from each group were killed after 1 d of continuous exposure, while the other half were killed after 7 d. Gross postmortem and histologic examinations were conducted on each dog. No obvious 2,4-D effects were detected in any of the dogs.

2,4-Dichlorophenoxyacetic Acid↗

PubMed1976

Effects of 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide and its metabolites on Novikoff hepatoma cells.

Studies were undertaken to determine the effects of 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) and its metabolites on the growth and macromolecular synthesis of Novikoff hepatoma cells in culture. DTIC (3.0 mM) in light decreased the viable cell count by 90% within 96 hr. DTIC protected from light, 2-azahypoxanthine, dimethylamine, and 5-aminoimidazole-4-carboxamide, all at 3.0 mM, reduced the rate of cellular proliferation. 5-Diazoimidazole-4-carboxamide (1.0 mM) and 5-(3-methyl-1-triazeno)imidazole-4-carboxamide (3.0 mM) decreased the viable cell count by 99%. Effects on macromolecular synthesis were determined by the rate of incorporation of the appropriate 3H-labeled precursor. Results after 6 hr are given as percentage of controls. DTIC (1.0 mM) in light inhibited DNA (8%), RNA (41%), and protein (63%) synthesis. DTIC (1.0 mM) protected from light inhibited DNA (12%) and RNA (57%) synthesis. 5-Diazoimidazole-4-carboxamide (0.1 mM) inhibited DNA (1%), RNA (9%), and protein (1%) synthesis. 5-(3-Methyl-1-triazeno)imidazole-4-carboxamide (1.0 mM) inhibited DNA (72%) and protein (65%) synthesis but stimulated RNA (127%) synthesis. 2-Azahypoxanthine (1.0 mM) inhibited DNA (43%), RNA 82%) and protein (28%) synthesis. 5-Aminoimidazole-4-carboxamide (3.0 mM) stimulated DNA (354%) and RNA (266%) synthesis. These data show that DTIC is able to generate several toxic metabolites that may be responsible for its biological effects.

Animals↗

PubMed1976

[Inhibition of the cyclic AMP splitting myocardial nucleotide gydrolase by 5-methyl-7-diethylamino-s-triazol-(1,5-alpha)pyrimidine (rocornal)].

5-Methyl-7-diethylamino-s-triazolo-(1,5-alpha)pyrimidine (Rocornal, trapidil), which has been introduced in clinical medicine as a coronary vasodilatator, competitively inhibits the cyclic AMP splitting nucleotidehydrolase (phosphodiesterase) from the heart muscle. The K1 value for Rocornal is 0.14 +/- 0.016 mM. The enzyme inhibition by this compound is abolished after an exchange of the diethylamino-group in C-7 position against dimethylamine and chloride. The proved triazolo-pyrimidines were without effect on myocardial adenylate cyclase activity. It is concluded that the vasodilatory effect of Rocornal may be realized in smooth muscle cells by an inhibition of cyclic AMP breakdown.

Adenylyl Cyclases↗

PubMedDate not supplied

The formation, disposition, and hepatic metabolism of dimethylnitrosamine in the pig.

The disposition, metabolism, and endogenous formation of N-nitrosodimethylamine (NDMA) from nitrosatable precursors was studied in the intact pig and in animals with cannulated hepatic and portal veins and catheterized bile ducts. Rates of disappearance of NDMA from peripheral venous and arterial blood after iv injections were virtually identical and the compound appeared in bile after a lag time of about 1 hr, with a subsequent decline in biliary concentration at about the same rate as in circulating blood. Measurements of NDMA in portal and hepatic vein blood after oral doses of 10, 1.0 and 0.1 mg/kg, respectively, showed progressively greater hepatic extraction with levels in the hepatic vein approaching the limits of detection after the lowest dose. Both halothane and ethanol virtually abolished the hepatic extraction of NDMA, presumably due to their known inhibitory action on its metabolism in the liver. Endogenous formation of NDMA and N-nitrosomorpholine after oral doses of the amines plus nitrite was demonstrated by their detection and measurement in the portal vein blood. Morpholine was nitrosated more effectively than dimethylamine and inhibited the nitrosation of the latter when the two amines were given together. NDMA was found in the portal blood after sequential oral administration of aminopyrine and nitrite, the concentration being considerably greater after fasting for 24 hr than after a 2-hr fast when much food was present in the stomach.

Aminopyrine↗

PubMed1990

Omega-dialkylaminoalkyl ethers of 3-exo-dialkylamino-(Z)-camphoroximes with antiarrhythmic and local anesthetic activities.

The synthesis of 3-exo-dialkylamino-(Z)-camphoroximes 7 starting from a mixture of 3-endo- and 3-exo-bromocamphornitrimine, hydroxylamine hydrochloride and excess secondary amine (dimethylamine, pyrrolidine, piperidine or morpholine) is described. Compounds 7 gave a series of omega-dialkylaminoalkyl ethers 9, 10 and 11 by reaction of 7 as sodium salts with omega-chloroalkyldialkylamines in DMF solution. Some of compounds 9, 10, 11 showed an appreciable antiarrhythmic and local anesthetic activity in rats and mice, respectively.

Amines↗

PubMed1990

Characterization of muscarinic M4 binding sites in rabbit lung, chicken heart, and NG108-15 cells.

We have carried out an extensive pharmacological characterization of muscarinic binding sites in rabbit lung and chicken heart in parallel with M1, M2, and M3 sites, [3H]Pirenzepine, a selective antagonist at M1 receptors, bound saturably and reversibly to membranes from chicken heart and rabbit lung. These binding sites were not M1 receptors, however, because the cardioselective antagonist himbacine had 10-fold higher affinity at these sites than at [3H]pirenzepine sites in rat and rabbit cortex (true M1 sites). We measured the inhibitory potency of 28 antagonists at [3H]N-methylscopolamine-labeled sites in chicken heart, rabbit lung, rat heart (M2 sites), and rat submandibular gland (M3 sites) and at M1 sites in rat cortex. The sites in rabbit lung were different from M1, M2, and M3 sites, because they had moderate to high affinity for M1-selective compounds (pirenzepine and telenzepine), M2-selective compounds (himbacine and methoctramine), and M3-selective compounds (hexahydrosiladifenidol and 4-diphenylacetoxy-N-methylpiperidine methiodide). The sites in chicken heart resembled most those in rabbit lung, with similar high affinity for secoverine, but they were not the same because tropicamide, diphenylacetoxybutynyl dimethylamine, and [3H]-N-methylscopolamine were more potent in rabbit lung. In a further series of experiments, we compared the affinity of six of the most discriminating antagonists in membranes from rabbit lung and NG108-15 cells, a neuroblastoma-glioma cell line reported to express the muscarinic m4 receptor gene. The antagonists had very similar affinities in the two tissues, the largest discrepancy being that pirenzepine was twice as potent in rabbit lung as in NG108-15 cells. Northern blots using probes designed to discriminate between five species of muscarinic receptor RNA detected only m4 mRNA in rabbit lung. We conclude that rabbit lung contains a muscarinic M4 binding site with a quite distinctive pharmacology and that chicken heart contains a receptor with similarities to the M4 sites. This is the first report to characterize native M4 binding sites in a nonneuronal mammalian tissue.

Animals↗

PubMedDate not supplied

[Effect of nitrosodimethylamine at various concentrations on various enzymatic systems in rat kidney endoplasmic reticulum and mitochondria depending on the duration of drug action].

Dissimilar response of rat kidney microsomal and mitochondrial enzymes was observed after administration of nitrosodimethylamine at concentrations 0.1, 1.0 and 10.0 mg/L within 2, 5 and 10 months. Activity of the mitochondrial enzymes studied depended to a greater degree on concentration of the drug administered as compared with duration of its effect. At the same time, activity of the microsomal enzymes studied was increased depending on duration of nitroso-++ dimethylamine action administered at concentration of 0.1 mg/L, while it did not alter if concentration of the drug was increased from 1.0 to 10.0 mg/L within the all periods of examination.

Animals↗

PubMed1989

Spectroscopic characterization of secondary amine mono-oxygenase. Comparison to cytochrome P-450 and myoglobin.

Secondary amine mono-oxygenase from Pseudomonas aminovorans catalyzes the NAD(P)H- and dioxygen-dependent N-dealkylation of secondary amines to yield a primary amine and an aldehyde. Heme iron, flavin, and non-heme iron prosthetic groups are known to be present in the oligomeric enzyme. The N-dealkylation reaction is also catalyzed by the only other heme-containing mono-oxygenase, cytochrome P-450. In order to identify the heme iron axial ligands of secondary amine mono-oxygenase so as to better define the structural requirements for oxygen activation by heme enzymes, we have investigated the spectroscopic properties of the enzyme. The application of three different spectroscopic techniques, UV-visible absorption, magnetic circular dichroism and electron paramagnetic resonance, to study eight separate enzyme derivatives has provided extensive and convincing evidence for the presence of a proximal histidine ligand. This conclusion is based primarily on comparisons of the spectral properties of the enzyme with those of parallel derivatives of myoglobin (histidine proximal ligand) and P-450 (cysteinate proximal ligand). Spectral studies of ferric secondary amine mono-oxygenase as a function of pH have led to the proposal that the distal ligand is water. Deprotonation of the distal water ligand occurs upon either raising the pH to 9.0 or substrate (dimethylamine) binding. In contrast, the deoxyferrous enzyme appears to have a weakly bound nitrogen donor distal ligand. Initial spectroscopic studies of the iron-sulfur units in the enzyme are interpreted in terms of a pair of Fe2S2 clusters. Secondary amine mono-oxygenase is unique in its ability to function as cytochrome P-450 in activating molecular oxygen but to do so with a myoglobin-like active site. As such, it provides an important system with which to probe structure-function relations in heme-containing oxygenases.

Circular Dichroism↗

PubMed1989

Purification and properties of a new enzyme, NG,NG-dimethylarginine dimethylaminohydrolase, from rat kidney.

A new enzyme, NG, NG-dimethylarginine dimethylaminohydrolase which plays a role in the metabolism of NG,NG-dimethyl-L-arginine, has been purified to homogeneity from rat kidney. The enzyme consists of a single polypeptide and its molecular weight is about 33,000. The isoelectric point of the enzyme is at pH 5.2. The enzyme catalyzes the hydrolytic liberation of the dimethylamino moiety of NG,NG-dimethyl-L-arginine and forms L-citrulline and dimethylamine. It is highly specific for NG,NG-dimethyl-L-arginine and NG-monomethyl-L-arginine, and the Km values for these amino acids are 0.18 and 0.36 mM, respectively. The enzyme shows the maximum activity at pH 6.5 and requires no cofactor. The activity is strongly inhibited by SH-blocking reagents (e.g. p-chloromercuribenzoate and HgCl2) and divalent metal ions (e.g. Cd2+, Cu2+, and Zn2+).

Amidohydrolases↗

PubMed1989

[Effect of lignins and their model compounds on amine nitrosation in a human gastric juice medium and in the body of mice].

The study was concerned with the influence of lignins of leaf-bearing and coniferous timber and 22 model compounds (lignin components) on nitrosation of dimethylamine, amidopyrine and morpholine in human gastric juice. Some results of the study were confirmed in murine experiments. Compounds of the guaiacyl series showed the highest inhibitory activity. Lignins of coniferous timber proved most effective.

Animals↗

PubMed1978

Mechanism of N-nitrosodimethylamine formation from trimethylamine and trimethylaminoxide.

The kinetics of nitrosation of trimethylamine (TMA) and trimethylaminoxide (TMAO) to give N-nitrosodimethylamine (NDMA) have been studied. The nitrosation rates of TMA and TMAO, when determined at 100 degrees C in sealed tubes, showed maximum values at about pH 3, while at temperatures lower than 75 degrees C the pH dependence of the nitrosation of these compounds was similar to that observed with alkylamides. The initial rate of NDMA formation from TMAO determined at pH 3.0 and 25 degrees C was found to be proportional to the TMAO and nitrite concentrations, not to the square of the nitrite concentration. In contrast, the rates of NDMA formation from TMA and TMAO when reacted at pH 3.0 and 100 degrees C in sealed tubes were found to be proportional to the square and the cube, respectively, of the nitrite concentration. These results strongly suggest that the NDMA formation at higher temperatures involves the oxidative cleavage of tertiary amines to produce secondary amines (dimethylamine, DMA) which may react with nitrite to form NDMA. On the other hand, at lower temperatures, NDMA may be formed from TMA or TMAO by a pathway not involving DMA.

Chemical Phenomena↗

PubMed1978

Preliminary observations on amines and nitrosamines in non-normal human gastric contents.

Gastric contents from fasting humans were pooled and analysed for amines. Volatile amines present were dimethylamine, trimethylamine and histamine; non-volatile amines found were cadaverine, putrescine, ethanolamine and tryptamine. Gastric contents from 35 patients, some before and/or after gastric stimulation with histamine or pentagastrin, were analysed for nitrosamines. N-Nitrosodiethylamine (NDEA) (5-30 microgram/kg) was present in four samples, N-nitrosodimethylamine (NDMA) (2 microgram/kg) in two samples and N-nitrosopyrrolidine (NPYR) (6 microgram/kg) in one sample. pH, nitrite and nitrate determinations were made on some samples. Medical diagnosis of patients could not be correlated with the presence of nitrosamines in the gastric contents.

Amines↗

PubMedDate not supplied

Pharmacokinetics and metabolism of the antitumor drug amonafide (NSC-308847) in humans.

Pharmacokinetics and urinary excretion of Amonafide (5-amino-2-[2-(dimethylamine)ethyl]-1H-benz[de]isoquinoline-1,3-(2H)- dione) were examined in seven patients who were administered 400 mg/m2 of drug as a 30-min infusion on a daily schedule for 5 consecutive days. Amonafide concentrations in plasma and urine were determined using reversed phase HPLC. Amonafide was eliminated from plasma with a terminal half-life of 3.5 hr. Renal excretion accounted for 23% of the administered dose. Amonafide pharmacokinetic parameters after the initial dose (day 1) were similar to those calculated after the fifth daily dose. Amonafide undergoes a significant amount of metabolism and eight urinary metabolites have been identified using a thermospray liquid chromatography-mass spectrometry (LC/MS) technique. Various N-acetylated species appear to be the major metabolites, although no evidence of N-acetylation was found in urine obtained from two patients. Two of the primary metabolites, the N(N5)-acetyl and N'(N1)-oxide metabolites of Amonafide, were tested in vitro for cytotoxicity against P388 murine leukemia cells. In this test system, the N-acetyl metabolite was observed to be only slightly less cytotoxic than the parent compound. The N'-oxide of Amonafide, however, proved to be inactive. These results are discussed together with the pharmacokinetic and metabolism data of this new investigational antitumor drug.

Adenine↗