[Nitrosamine formation from pyrazolone derivatives?].
Explore the source record for details and available documents.
Aminopyrine↗
SEARCH · Search PubMed
Results for “Pyrazolones”
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.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
[Nitrosamine formation by pyrazolone derivatives?].
Explore the source record for details and available documents.
Aminopyrine↗
Synthesis of new pyrazolones as potent anti-inflammatory agents.
Explore the source record for details and available documents.
Animals↗
Non-steroidal anti-inflammatory agents. 4-[1-(3, 5-disubstituted-2-thio-thio-1,3,5-perhydrotriazinyl)]-2,3-dimethyl-1-phenyl-5-pyrazolones.
Several derivatives of pyrazolo-s-perhydrotriazine-2-thione were synthesized. The IR and MS of representative compounds are interpreted. The preliminary results of the anti-inflammatory test on female albino rats indicate that the compounds under test are more potent than phenylbutazone and do not produce any marked degree of ulceration.
Animals↗
The effects of antipyretics on metabolism processes in rat liver mitochondria. Part I. The action of sodium salicylate, and pyrazolones on the reaction of respiratory chain.
The effects of sodium salicylate (SS), phenazone (Ph) and aminophenazone (APh) on mitochondrial respiration respiration and oxidative phosphorylation were studied in vitro, SS inhibited state 3 but stimulated state 4 of respiration, if alpha-ketoglutarate and succinate were used as the substrates. The inhibition of state 3 of respiration was not reversed by 2,4-dinitrophenol (DNP). Ph and APh inhibited the respiratory state 3 without affecting the state 4 in the presence of the same substrates, and the produced inhibition in state 3 was reversible by DNP. Studies on ATP synthesis have revealed that SS was the only antypyretic tested that exerted an uncoupling action. SS stimulated the mitochondrial ATPase activity but inhibited it after uncoupling of oxidative phosphorylation with DNP. The mitochondrial ATPase activity remained uninfluenced by Ph or APh. The only similar action of all the drugs investigated was the inhibition of oxidation in the respiratory state 3.
Adenosine Triphosphatases↗
[Mechanism of the hypobilirubinemic effect of prednisolone and some pyrazolone derivatives].
The effects of prednisolone (1 mg/kg), nicophezone (10 mg/kg), phenylbutazone 30 mg/kg) and antradion (60 mg/kg) on choleresis and bilirubin passage with bile was studied in intact and CCl4-poisoned rats (by using hemolyzed blood loads). Intravenous administration of hemolyzed blood to intact animals was shown to be attended by an increased excretion of bilirubin with the bile. When superimposed upon the CCl4 poisoning--the excretion of bilirubin diminishes. The study compounds stimulated the passage of bilirubin with the bile following introduction of hemolyzed blood both in intact animals and in the ones with the CCl4-damaged liver. The data thus made available are used in interpreting the mechanism underlying the hypobilirubinemic effect of the compounds.
Animals↗
The effects of antipyretics on metabolic processes in rat liver mitochondria. Part II. The action of sodium salicylate, and pyrazolones on oxidation of alpha-ketoglutarate.
The effect of sodium salicylate (SS), phenazone (Ph), and amiphenazone (APh) on the uptake of alpha-ketoglutarate (alpha-KG) by the rat liver mitochondria was studied in vitro. The investigated antipyretics inhibited the uptake of alpha-KG in the state 3 of respiration, and significantly increased it in state 4. This results and those of the preceding paper show that alpha-KG taken up by the mitochondrial preparations in respiratory state 4 is not utilized in the oxidative processes of the respiratory chain.
Aminopyrine↗
[Extraction of pyrazolone-5 derivatives with the aid of partition paper chromatography].
Explore the source record for details and available documents.
Chemical Phenomena↗
[Urticaria--angioedema induced by non-steroidal anti-inflammatory analgesics].
Forty-two adult patients had been evaluated with a history of Urticaria and Angioedema (U-AE) associated with ingestion of non-steroidal anti-inflammatory drugs (NSAID). None developed attacks of bronchospasm. None had chronic urticaria. The same reaction was repeated in 36 individuals on at least two different occasions following administration of these drugs. Based on patients'history we distinguished three groups: Group A: twenty-three patients who had presented U-AE with the administration of pyrazolone drugs. Thereafter, sixteen of them had taken aspirin without adverse reactions. Group B: Nine patients in whom aspirin caused U-AE, after three of them had taken pyrazolone drugs without intolerance. The remaining six had not taken analgesic drugs since the last reaction. Group C: Ten patients who had developed U-AE with aspirin as well as with pyrazolone drugs. The objective of our study was the following: 1) to observe tolerance level of these patients to other NSAID different from those which had produced the first reactions. 2) To test to see if the patients who had suffered U-AE by noramidopyrine and aminophenazone tolerated other pyrazolone drugs like sulfinpyrazone and phenylbutazone. 3) To see if reactions are produced with tartrazine in patients who had presented U-AE with pyrazolone drugs, given that this colouring (tartrazine) is a pyrazolone derivative. Skin test (prick and intracutaneous test) with noramidopyrine, phenylbutazone and noramidopyrine metasulphonate MG, were carried out on the patients in group A, group C and 30 normal controls. In all the groups oral challenge tests were performed with progressive doses of naproxen, indomethacin, paracetamol, ciclofenac, mefenamic acid, piroxicam and phenylbutazone. Oral challenge tests were accomplished with aspirin in group A and with propiphenazone in group B. Oral challenge tests with sulfinpyrazone and tartrazine were also performed on various patients in group A and group C. The interval between the administration of progressive doses of a drug was 3 and as half hours and were allowed to pass at least 24 hours before testing other different analgesics. The test was considered positive if cutaneous rash, wheals, AE or hypotension were produced. In this case, the test was halted and 7 days were allowed to pass before continuing the study with a new drug. Based on the oral challenge tests performed, three types of patients could be distinguished: 1) individuals sensitive only to the pyrazolone drugs and who can take with impunity other NSAID.(ABSTRACT TRUNCATED AT 400 WORDS)
Administration, Oral↗
Electrochemistry and kinetics of fungal laccase mediators.
The screening of potential redox mediators for laccase was performed using homogeneous Trametes hirsuta laccase. Heterogeneous (electrochemical) and homogeneous (oxidation by laccase) reactions of the different types of the enhancers (mediators) of the enzyme were investigated. It was discovered that derivatives of phenyl-methyl-pyrazolones and benzoic acid, as well as N-hydroxynaphthalimide were efficient substrates for the laccase. The characterization of several representatives from each class was carried out using electrochemical and enzyme kinetics methods. The kinetic parameters for the oxidation of phenyl-methyl-pyrazolones and 3-(6-hylroxy)-aminobenzoic acid were comparable to those for 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonate) (ABTS) oxidation by the laccase, whereas the rate of enzymatic oxidation of N-hydroxynaphthalimide was sufficiently lower. Electrochemical experiments demonstrated that only oxidation of phenyl-methyl-pyrazolones and N-hydroxynaphthalimide yielded several high-potential intermediates capable of oxidizing veratryl alcohol, which was used as a lignin model substrate, whereas derivatives of benzoic acid showed low-potential intermediate, which was not able to oxidized lignin model compound. Phenyl-methyl-pyrazolones was about 50% as effective in degrading veratryl alcohol compared to ABTS as judged from HPLC kinetic studies, whereas N-hydroxynaphthalimide showed the same efficiency as ABTS. Phenyl-methyl-pyrazolones and hydroxynaphthalimides may be of commercial interest for oxidoreductase-catalyzed biodegradation of different xenobiotics.
Basidiomycota↗
Calcium-sensing soluble adenylyl cyclase mediates TNF signal transduction in human neutrophils.
Through chemical screening, we identified a pyrazolone that reversibly blocked the activation of phagocyte oxidase (phox) in human neutrophils in response to tumor necrosis factor (TNF) or formylated peptide. The pyrazolone spared activation of phox by phorbol ester or bacteria, bacterial killing, TNF-induced granule exocytosis and phox assembly, and endothelial transmigration. We traced the pyrazolone's mechanism of action to inhibition of TNF-induced intracellular Ca2+ elevations, and identified a nontransmembrane ("soluble") adenylyl cyclase (sAC) in neutrophils as a Ca2+-sensing source of cAMP. A sAC inhibitor mimicked the pyrazolone's effect on phox. Both compounds blocked TNF-induced activation of Rap1A, a phox-associated guanosine triphosphatase that is regulated by cAMP. Thus, TNF turns on phox through a Ca2+-triggered, sAC-dependent process that may involve activation of Rap1A. This pathway may offer opportunities to suppress oxidative damage during inflammation without blocking antimicrobial function.
Adenylyl Cyclases↗
Novel laccase redox mediators: spectral, electrochemical, and kinetic properties.
The screening of potential redox mediators for laccase was performed using homogeneous enzyme preparations from Coriolus hirsutus and Coriolus zonatus. It was discovered that derivatives of 1-phenyl-3-methyl-pyrazolones were efficient substrates for the laccases. The characterization of two representatives of the 1-phenyl-pyrazolone class, sodium 1-phenyl-3-methyl-4- methylamino-pyrazolone-5-N(4)-methanesulfonate and 1-(3'-sulfophenyl)-3- methylpyrazolone-5, in the reaction catalyzed by laccase was carried out using spectral, electrochemical, and enzyme kinetics methods. The kinetic parameters for the oxidation of the newly discovered substrates were comparable with those for 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonate) (ABTS) oxidation by laccase. Electrochemical experiments demonstrated that oxidation of these compounds yielded two high-potential intermediates capable of oxidizing veratryl alcohol, which was used as a lignin model substrate, to the corresponding aldehyde and acid. 1-(3'-Sulfophenyl)-3- methylpyrazolone-5 was about 30-40% as effective in degrading veratryl alcohol compared to ABTS as judged from high-performance liquid chromatography kinetic studies. 1-Phenyl-3-methyl-pyrazolones may be of commercial interest for oxidoreductase-catalyzed biodegradation of organic compounds.
Basidiomycota↗
[Thoracic epidural analgesia (TEA) with morphine as an alternative to the administration of general anesthesia in thoracotomized patients].
A randomised prospective study was conducted into 60 patients who had undergone thoracotomy for spontaneous pneumothorax or bronchial carcinoma. Pyrazolone was intramuscularly and intravenously injected for postoperative pain relief to some of these patients. Another group received morphine through an epidural catheter (TEA). Postoperative spirometric checks were made on the first, third, and fifth days from surgery. The degree of analgesia was measured by means of the Twycross method. The ventilation parameters recorded from patients with epidural morphine treatment were clearly better than those measured from patients who had received pyrazolone. The amount of pain relief reported by TEA patients were better than that recorded from the pyrazolone group.
Adult↗
Substituted 4-acylpyrazoles and 4-acylpyrazolones: synthesis and multidrug resistance-modulating activity.
A series of 4-acyl-3-pyrazolone derivatives with a 3-substituted 2-hydroxy-3-aminopropyl chain attached to pyrazole N-1 (7-20) as well as isomeric 4-acyl-5-(3-substituted 3-amino-2-hydroxypropoxy)pyrazole derivatives (5, 6) were synthesized, and their multidrug resistance (MDR)-modulating activity was measured using the daunomycin efflux assay. Reaction of N1-substituted 4-acyl-3-pyrazolones (tautomer to 4-acyl-5-hydroxypyrazoles) with excessive epichlorohydrin and successive treatment with an appropriate amine resulted in N-alkylation and thus afforded the target pyrazolone derivatives 7-20. In contrast, O-alkylation occurred upon reaction with 1 equiv of epichlorohydrin and subsequent treatment with amine leading to the corresponding 4-acyl-5-pyrazolyl ethers 5 and 6. QSAR studies showed a good correlation of MDR-modulating activity with lipophilicity of the compounds. Inclusion of hydrogen bond acceptor strength and steric parameters as descriptors led to a QSAR equation with remarkably increased predictive power (r2cv = 0.92). Additionally, ortho substitution of the propanolamine side chain and the acyl moiety is favorable. Detailed NMR spectroscopic investigations were carried out with the title compounds.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
[Effects of analgesic-antipyretics on the spinal reflex potentials in cats: an analysis of the excitatory action of aminopyrine].
The effects of some analgesic-antipyretics on the spinal reflex potentials were studied in spinal cats. Aminopyrine at 25-100 mg/kg, i.v. produced a marked increase in mono- and poly-synaptic reflex potentials (MSR and PSR), and a decrease in dorsal root reflex potentials (DRR) in a dose-dependent manner. The amplitude of DRR decreased by aminopyrine was reversed by diazepam at 0.2 mg/kg, i.v.; however, the increased amplitudes of MSR and PSR were not affected by diazepam. Pretreatment of semicarbazide at 200 mg/kg, i.v. did not influence the increasing effect of aminopyrine on MSR and PSR. DL-5-Hydroxytryptophan produced facilitation of the MSR and PSR. In DL-5-hydroxytryptophan-treated cats, the amplitude of MSR was further increased by aminopyrine. Methysergide at 1 mg/kg, i.v. antagonized this increasing effect of aminopyrine on MSR and PSR. These observations suggest that the excitatory action of aminopyrine may be partly related to 5-hydroxytryptamine and not connected to the GABAergic mechanism. Other pyrazolone derivatives were also studied. Isopropylantipyrine at 50 mg/kg, i.v. produced increases in MSR and PSR. Intravenous sulpyrine at 500 mg/kg, antipyrine at 50 mg/kg or 4-aminoantipyrine at 50 mg/kg did not affect the reflex potentials. The non-pyrazolones, acetaminophen and indomethacin, did not increase the MSR and PSR. These results suggest that the N-dimethyl or isopropyl residue at the 4 position of the pyrazolone structure plays an important role in the excitatory action of analgesic-antipyretics in cat spinal cord.
5-Hydroxytryptophan↗
[Drug allergy damage to the blood ].
Drug induced blood dyscrasias, leukocytopenia, thrombocytopenia and hemolytic anemia were observed in 7% of 643 adverse drug reactions registered by drug monitoring in Bern, Switzerland, in the period 1970-1973. Life threatening reactions were consistently more frequent in hematological side effects (22%) than in the total of adverse drug reactions (6%). Blood dyscrasias induced by drug allergy are generally believed to belong to the allergic reactions of type II. Antigen-antibody reaction evolves in connection with cells of the blood, either by fixation of the drug itself or a metabolite on the cell surface, or by adsorption of primarily formed antigen-antibody complexes on the cell. In drug induced immune hemolytic anemia three types may be distinguished: 1. the innocent bystander type, caused by quinine, PAS, rifampicin and others, 2. the penicillin-type, caused by penicillins and cephalosporins, and 3. the autoimmune type caused by alpha-methyl-dopa etc. Agranulocytosis in Europe is most frequently due to pyrazolones, while phenothiazines play the leading role in the USA. In pyrazolone agranulocytosis an allergic pathogenesis is very probable, whereas phenothiazines probably induce agranulocytosis by a direct toxic effect on bone marrow cells. The clinical course in pyrazolone agranulocytosis is acute, whereas it is rather insidious in the phenothiazine type. The main drugs causing allergic thrombocytopenia are thiazide diuretics, quinine, quinidine and sulfonamides. Clinical aspects and therapy of drug induced blood dyscrasias are discussed.
Agranulocytosis↗
[Study of drug allergies with special reference to skin manifestations].
One hundred and forty four patients, with dermal reactions to different drugs, were chosen from our clinic. The selection criteria was based on a detailed and careful anamnesis in order to be certain of the specific drug responsible for the reaction. We tried to establish a drug-specific reaction pattern for each of the drugs studied. Intradermal skin tests were performed with all drugs to be studied, except with pyrazolones and aspirin, for which patch tests were applied. The drug concentrations were established prior to the tests in order to avoid unwanted unspecific reactions. In every case, immediate and delayed reaction readings were carried out. A three crosses reaction (+++) was considered positive. The skin tests were positive in 44% of the cases, a value higher than those referred to by most authors. The delayed reactions to skin tests and the chloramphenicol-mediated delayed-type "dermatitis-like" manifestations are compared. It is noteworthy to mention that positive delayed reactions were observed more frequently with chloramphenicol than with any of the other studied drugs. The same applies for those patients with a positive history to chloramphenicol. The most common reaction pattern to penicillin and streptomycin in our series (20%) were urticaria and Quincke's edema. Penicillin, pyrazolones and streptomycin were the most common drugs responsible for urticarial patterns, being the pyrazolones related to fixed erythema in many cases. The age group 25-50 was the most frequently involved. No sex predominance was observed. The value of the classic skin tests is discussed, so are history recording and the in vitro tests.
Adolescent↗
[Degradation of antipyrin by pyrazon-degrading bacteria (author's transl)].
Bacteria with the ability to grow on pyrazon as sole source of carbon were isolated from soil. They also are able to grow on antipyrin. Then three metabolites of antipyrin can be isolated from the culture fluid which were identified as 2,3-dimethyl-1-(cis-2,3-dihydro-2,3-dihydroxy-4,6-cyclohexadiene-1-yl)-pyrazolone (5) (I), as 2,3-dimethyl-1-(2,3-dihydroxyphenyl)-pyrazolone (5) (II) and as 2,3-dimethyl-pyrazolone (5) (III), respectively. Compound I and II were used as substrates for enzyme studies. A dioxygenase catalyzes the enzymatic conversion of antipyrin into compound I. In the presence of NAD as cosubstrate compound I is transformed into compound II by a dehydrogenase. A pure preparation of metapyrocatechase from pyrazon-degrading bacteria converts compound II into the dephenylated heterocyclic moiety of antipyrin (III) and into 2-pyrone-6-carboxylic acid. Based on the results of the enzymatic studies a pathway for the degradation of antipyrin is proposed.
Antipyrine↗