PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Pyrazolones”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 19 recordsLinked to original sources
PubMed1975

[Combined use of bucolome and pyrazolone derivatives (II). Complex formation due to interaction between bucolome and pyrazolones].

We have already reported that bucolome (BCP), a non-steroidal anti-inflammatory agent, potentiates significantly the analgesic and antipyretic effects of pyrazolones which are substituted by alkylamino group at 4-position of the pyrazolone ring. Physical and quantum chemistry were applied to the mechanism of this synergistic action. The solubility of BCP was markedly increased in proportion to elevation of aminopyrine (AM) concentration, but not by a combination with isopropylantipyrine (IP). The binding of BCP to bovine serum albumin was slightly inhibited by AM, but not by IP. The mixture of AM and BCP in aqueous media generated optical absorption in the ultraviolet differential spectrum, due to the charge transfer interaction. The results of the infrared or NMR spectrum demonstrated the formation of a hydrogen binding in non-aqueous media between BCP and AM. From the calculation of the charge on an atom, the energy of the highest occupied molecular orbital and the frontier electron density, BCP is considered to be a good electron acceptor. The beta-units of Mho of pyrazolones were found to correlate with the potentiation coefficient of analgesic activity in combination drugs. These results suggest that the complex formation between BCP and pyrazolones is an important factor for the synergism of action and is due to the charge transfer interaction and the hydrogen binding of both molecules.

Barbiturates↗
PubMed1986

Pyrazolone derivatives.

In many countries, the pyrazolone derivatives, which include dipyrone, antipyrine, aminopyrine and propyphenazone, are widely used analgesics. Dipyrone, the most widely used pyrazolone, has been the most studied. The pyrazolidine derivatives, phenylbutazone and oxyphenbutazone, which are not generally used for analgesia since they differ from the pyrazolones in terms of efficacy and tolerance, are not discussed in this article. Dipyrone is an inhibitor of cyclo-oxygenase but, unlike aspirin, its effect is rapidly reversible. The inhibition of prostaglandin biosynthesis contributes to the analgesic activity of the pyrazolone derivatives. Peak plasma concentrations of the pyrazolone derivatives generally occur 1 to 1.5 hours after oral administration. Half-lives vary from 1 to 2 hours with propyphenazone, to about 7 hours with dipyrone (2 hours for the active metabolite of dipyrone, 4-methylaminoantipyrine, MAA). Half-life of antipyrine varies considerably between individuals (5 to 35 hours). Unlike the NSAIDs generally, the pyrazolone derivatives antipyrine, aminopyrine and propyphenazone are minimally bound to plasma proteins. The pyrazolones undergo extensive biotransformation, aminopyrine and dipyrone being converted to active metabolites. Dipyrone is the only drug for which results of recent double-blind trials are available. Oral dipyrone has been shown to be more effective than an equal dose of aspirin or paracetamol in alleviating postoperative pain, and intravenous dipyrone 2.5g was similar in efficacy to pethidine 50 mg. In patients with acute ureteral or biliary colic, dipyrone 2.5g intravenously was similar in efficacy to indomethacin 50 mg or pethidine 50 mg. The most frequently reported side effects of the pyrazolone derivatives are skin rashes. Gastrointestinal side effects are rare. Blood dyscrasias, mostly associated with aminopyrine, have received wide attention in the medical literature, but their true incidence with dipyrone is considerably lower than the often quoted incidence for amidopyrine reported more than 30 years ago.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1975

[Combined use of bucolome and pyrazolone derivatives (1). Pharmacological activities and blood concentration].

A combination of two or more drugs may exert a drug-drug interaction, in which case the effect can be potentiated or antagonized. Such synergistic effects are well known in the case of pyrabital (barbital + aminopyrine) or irgapyrine (phenylbutazone + aminopyrine). Bucolome (BCP), a non-steroidal anti-inflammatory agent, has the chemical structure of a barbiturate and also resembles the formula of pheylbutazone. Thus the influence of BCP combination on the pharmacological activities of various pyrazolone derivatives was examined. BCP potentiated the analgesic and antipyretic effects of 4-aminoantipyrine (4A), methylaminoantipyrine (MA), aminopyrine (AM) and isopropylaminoantipyrine (IPA), which were substituted by the alkylamino group at 4-position of the pyrazolone ring. This potentiation occurred when the dose of BCP exceeded that of the pyrazolones, and was especially marked when combination ratio of BCP exceeded that of the pyrazolones, and was especially marked when combination ratio of BCP and pyrazolone was 2:1 mola. The analgesic effects of antipyrine (AN), isopropylantipyrine (IP) and aminopropylone (AP), which were substituted by alkyl group or aminoacylamino group at 4-position, were not potentiated by BCP in any combination ratio. Most pyrazolones showed additive acute toxicity in their combination with BCP, but acute toxicities of 4A and AM, which were potentiated in analgesic effects, were decreased and antagonized when combined with BCP. The plasma concentration of AM was increased and prolonged by BCP, while that of IP remained much the same. These results suggest that the pharmacological activities are associated with certain molecular interactions between BCP and pyrazolones, which are substituted by the alkylamino group at 4-position of the pyrazolone ring.

Analgesics↗
PubMed1986

[Clinico-immunological and allergological characteristics of urticaria caused by pyrazolone derivatives].

The authors describe the results of clinical, allergological and immunological examination of 35 patients with urticaria caused by pyrazolone derivatives. Clinically, the patients with pyrazolone-induced urticaria were marked by chronic diseases requiring the prolonged and frequent intake of the analgesics, pyrazolone derivatives. The allergological examination of the 35 patients with pyrazolone-induced urticaria showed that only one of the patients had pollenosis, 6 patients had IgG-mediated reactions to egg protein and one patient to penicillin. For specific diagnosis of drug allergy use was made of the natural leukocyte migration test in vivo according to A. D. Ado. The test appeared positive with analgin in all the 35 patients suffering from pyrazolone-induced urticaria. It represents a simple and accessible method for specific diagnosis of drug allergy both in inpatients and in those visiting allergological rooms at the polyclinics. The immunological examination made with the aid of the histograms demonstrated an appreciable reduction in the content of D-phagocytosing neutrophils. The latter fact might explain the presence of multiple chronic foci of infection in patients with pyrazolone-induced urticaria. Such patients manifested a decrease in C3 that might be related to immediate activation of the alternative pathway of complement by pyrazolone derivatives.

Adolescent↗
PubMed1998

Association of pyrazolone drug hypersensitivity with HLA-DQ and DR antigens.

BACKGROUND: In sensitive patients pyrazolone drugs can precipitate adverse reactions ranging from urticaria and angioedema to anaphylactic shock, presumably by immunological, IgE-mediated mechanism. However, up to now no genetic factors influencing the development of allergic reaction have been reported in this type of hypersensitivity. OBJECTIVE: The aim of our study was the investigation whether the susceptibility to development of pyrazolone drugs hypersensitivity (PDH) reactions was associated with HLA class II antigens. METHODS: To test this hypothesis we studied the distribution of HLA-DR and DQ antigens in 26 pyrazolone sensitive patients and control groups including unselected general population and clearly defined atopic and non-atopic groups. RESULTS: Significantly higher frequencies of DQ 7 and DR11 antigens were found in PDH group as compared with control unselected population (RR= 16.48, P < 0.0001; P(cor)< 0.002 and RR = 4.57, P = 0.0002; Pcor = 0.003 for DQ and DR antigen respectively). Similarly, statistically significant increased frequencies of DQ 7 and DR11 in patients with PDH were observed compared with atopic control group (RR= 18.43, P < 0.0001; Pcor <0.002 and RR= 6.33, P= 0.0007; Pcor =0.01, for DQ and DR antigen respectively). However, in comparison to non-atopic control group only the frequency of DQ 7 antigen was significantly increased (RR = 15.42, P = 0.0001; Pcor = 0.0015). DQ 7 antigen was present in 46.1% of PDH patients compared with 4.9%, 4.4% and 5.3% in the general population, atopic and non-atopic groups respectively, suggesting pyrazolone hypersensitivity as a trait positively correlated with this HLA antigen. CONCLUSION: Our data suggest a genetic predisposition to pyrazolone hypersensitivity reactions, linked to HLA-DQ locus.

Adolescent↗
PubMedDate not supplied

Diagnosis of pyrazolone drug sensitivity: clinical history versus skin testing and in vitro testing.

Pyrazolone drug hypersensitivity (PDH) may manifest as angioedema, urticaria, and/or life threatening anaphylactic shock. Although it has been suggested that PDH is an immunologic, probably IgE-mediated reaction, the diagnosis of PDH is still based on clinical history because there is no reliable in vitro diagnostic method currently used in clinical practice. The goal of this study was to evaluate the reliability of various methods to confirm a diagnosis of PDH. Twenty-eight patients with prior history of 71 reactions to pyrazolone drugs were studied. In all patients, pyrazolone drugs induced urticaria and angioedema. In addition, laryngeal edema occurred in 14 patients and anaphylactic shock with loss of consciousness in five patients. Skin prick test and intradermal tests using increasing concentrations of noraminophenazone were performed in 25 patients. Sera of all 28 patients were negative for pyrazolone-specific IgE as determined by an immunoenzymatic method. Peripheral blood mononuclear cells proliferative responses to pyrazolone were studied by a lymphocyte proliferation test with 3H-thymidine incorporation. Incubation of peripheral blood mononuclear cells with increasing concentrations of noraminophenazone did not induce any significant proliferation responses. Our study demonstrated that 1) intradermal skin tests correlate poorly with the clinical history of hypersensitivity reaction; and 2) in vitro tests are not useful in establishing a diagnosis of PDH.

Adolescent↗
PubMed1986

Does pyrazolone-induced renal injury exist?

On the basis of animal experiments and clinical findings, pyrazolones are found to have adverse renal effects. However, the latter are minor, very rare, and of practically no clinical relevance. In animals, pyrazolones induce proteinuria, oliguria, retention of substances excreted via the urine, and probably, in rare cases, papillary necrosis. Oliguria is rare in humans. A contribution of pyrazolone drugs in a specific case of papillary necrosis and in rare cases of acute interstitial nephritis is not proven, yet possible. Pyrazolone drugs induce renal injury less frequently than do the other classical analgesics.

Acute Kidney Injury↗
PubMed2000

A study of the fluorescence of some newly synthesized europium complexes with pyrazolone derivatives.

Some europium complexes with pyrazolone derivatives and 1,10-phenanthroline were synthesized and characterized. The europium ion was found to coordinate to O atoms of the pyrazolone derivatives and to N atoms of 1,10-phenanthroline. A strongly ligand-localized UV absorption leads to the europium-centered emissions between 580 and 750 nm which were assigned as the 5D0-->7F0,1,2,3,4 and 5D1-->7F3,4 transitions. A low site symmetry for the Eu3+ ion was confirmed from the observation of 5D0-->7F0 emission and from the splitting of the other bands. In contrast to many Eu complexes that have been investigated a rather weak emission was measured by introduction of a Schiff base to form a ternary complex with the pyrazolone derivative. The long fluorescence lifetimes of these complexes suggest an energy transfer process from ligands to Eu3+ ion through the triplet state of the ligands.

Europium↗
PubMed1983

[Contact urticaria caused by skin test in pyrazolone allergy].

About one third of patients with anaphylactic reactions to pyrazolones showed contact urticaria induced by to at least one pyrazolone after 30-60 min in patch test. This reaction was never observed in patients with various exanthemas or allergic contact dermatitis to these medicaments. Contact urticaria in patch test was mostly caused by propyphenazone, aminophenazone, and metamizole. The suspicious pyrazolone provoked positive results in only about 70%. No correlation could be found between contact urticaria in patch test and severity of allergic history, short interval before skin test and atopic constitution.

Adolescent↗
PubMed1983

Acute toxicity of pyrazolones.

Pyrazolone intoxication accounts for most (52 percent) mild analgesic poisonings in West Germany. Severe and fatal intoxication with pyrazolones is, however, rare. In the German literature, only 50 cases have been described in the past 62 years; 80 to 90 percent of these were caused by aminopyrine, which was withdrawn from the West German market in 1978 and replaced by propyphenazone. Up to now, no fatal poisoning with propyphenazone has been reported. However, the signs and symptoms of severe intoxication are similar for both propyphenazone and aminopyrine. The acute toxicity of dipyrone is slightly lower than that of propyphenazone, whereas phenylbutazone and oxyphenbutazone clearly cause less severe reactions. Characteristic symptoms include impaired consciousness progressing to coma, and convulsions. In addition, arrhythmia and cardiogenic shock may occur. Severe aminopyrine intoxication may also be complicated by sudden apnea. Liver damage may develop after a latent period of about 24 hours, especially after phenylbutazone and oxyphenbutazone poisoning. Therapy involves supportive measures as well as gastric emptying by emesis or lavage, installation of medical charcoal, and induction of diarrhea or gut lavage. Although exact clinicotoxicologic data on hemoperfusion are not available as yet, distribution volumes, plasma half-lives, and endogenous plasma clearances as well as results of in vitro trials all suggest the efficacy of this procedure. Hemoperfusion with uncoated amberlite XAD-4 resin is, therefore, recommended for patients with severe pyrazolone intoxication.

Acute Disease↗
PubMed1980

Further production and characterization of antibodies reactive with pyrazolone derivatives.

A sensitive radioimmunoassay for pyrazolone derivatives has been developed. Anti-antipyrine antisera were produced in rabbits by repeated immunization with 4-succinamidoantipyrine coupled to bovine serum albumin. Less than 1 ng of antipyrine could be detected by this procedure. Various substituents on the carbon-4 position of the pyrazolone ring decreased the affinity for the antibody. The concentrations in ng of various pyrazolone derivatives required to inhibit [3H]antipyrine binding by 50% were: antipyrine, 6.8; aminopropylon, 8.5; sulpyrine, 35.5; isopropylantipyrine, 1320; and aminopyrine, 2820. The antibody showed no cross-reactivity with any other antipyretics such as pyrazolidine or aniline derivatives. The determination of antipyrine and sulpyrine concentrations in rat serum after i.p administration was also carried out.

Aminopyrine↗
PubMed1983

[Effect of pyrazolone derivatives on the level of reduced glutathione in rat liver].

The pyrazolone derivatives aminophenazone, phenazone, and propyphenazone are capable of decreasing reduced glutathione (GSH) in the liver after a single dose of 3 mmol/kg. The strongest effect is seen in female animals treated with propyphenazone. The depletion can be caused by (1) consumption during phase I of biotransformation, if reactive side products are inactivated by GSH-peroxidase, (2) consumption during phase II of biotransformation, if reactive metabolites are conjugated with GSH by GSH-S-transferases, (3) consumption of NADPH during the biotransformation processes of the pyrazolones as such, (4) influence on enzymes responsible for the synthesis of GSH. After repeated administration only aminophenazone decreases the hepatic content of GSH. Pretreatment with phenobarbital only prevents the propyphenazone-dependent GSH-depletion, but cobaltous chloride has no effect. GSH-depletion is regarded as one of the primary events in liver damage, following pyrazolone administration.

Aminopyrine↗
PubMed1998

Mutagenicity assay in Salmonella and in vivo sister chromatid exchange in bone marrow cells of mice for four pyrazolone derivatives.

Phenylbutazone (PB), oxyphenbutazone (OPB), antipyrine (AP) and dipyrone (DP) are four important pyrazolone derivatives mainly used as anti-inflammatory, antipyretic and analgesic drugs. At present these are the most widely used pyrazolone derivatives throughout the world. The widespread use of these drugs are of great concern for human health problems. In the present study these four drugs were tested in mutagenicity assays in Salmonella strains TA97a, TA98, TA100 and TA102 using a plate incorporation assay both with and without S-9 mix and for in vivo sister chromatid exchanges (SCE) in bone marrow cells of mice. The first three drugs were negative in all the tester strains but dipyrone showed a weak mutagenic activity at higher concentrations in all four strains both with and without metabolic activation. In the in vivo SCE assay in male mice, all four drugs showed a statistically significant increase in SCE in bone marrow cells when compared with control.

Animals↗
PubMed1979

Radioimmunoassay for pyrazolone derivatives.

The determination of pyrazolone derivatives by radioimmunoassay has been reported. Anti-antipyrine antisera were obtained by repeated immunization of rabbits with 4-azoantipyrine-conjugated bovine serum albumin. The level at least as low as 1.0 ng of antipyrine could be detected by this procedure. Various substituents on the carbon 4 position of the pyrazolone ring as well as the lack of methyl group on the nitrogen 2 position decreased the affinity for the antibody, and the antibody showed no cross-reaction with any pyrazolidine derivatives.

Ampyrone↗
PubMed1987

Investigation of an alkylamine modified and pH-controlled mobile phase for separation of pyrazolone derivatives by high-performance liquid chromatography.

The separation of pyrazolone derivatives with different acid-base properties and polarities has been investigated in view of recent concepts about the retention mechanisms in reversed-phase liquid chromatography. It is shown that both the protonated (BH+) and uncharged (B) bases undergo a dual mechanism of retention due to solvophobic and silanophilic interactions. The latter are easily suppressed by the addition of an alkylamine modifier (dibutylamine) to the mobile phase. An ion-pairing mechanism is found to be valid in the retention of negatively charged (A-) pyrazolone derivatives, since the dibutylamine modifier (BH+) serves as an appropriate counter ion. The behaviour of these solutes can be predicted from the pH dependence of their capacity factors, and a new simple method is proposed for calculating the theoretical sigmoidal curves. It is shown that the elution order of the compounds can be changed by control of both the pH value and the modifier concentration in the mobile phase.

Ampyrone↗
PubMed2002

Synthesis of spiro-fused (C5)-isoxazolino-(C4)-pyrazolones (1-oxa-2,7,8-triazaspiro[4,4]-2,8-dien-6-ones) via 1,3-dipolar cycloaddition and cycloelimination.

An efficient and selective method for the synthesis of spiro-fused (C5)-isoxazolino-(C4)-pyrazolones (C) is reported. The process consists of utilizing the Baylis-Hillman reaction-or a quicker, stepwise MAC procedure-to give I followed by 1,3-dipolar cycloaddition and Swern oxidation to give beta-ketoesters H, which were condensed with hydrazine derivatives to provide hydrazones that underwent cycloelimination. These novel spiro-fused (C5)-isoxazolino-(C4)-pyrazolones were confirmed by spectroscopic analysis as well as single-crystal X-ray of 5. We also concluded that all condensations/cycloeliminations, except with hydrazine itself, were more effective with catalysts or higher reaction temperatures. For example, TiCl(4) was an efficient catalyst for hydrazone formation and cycloelimination with methylhydrazine, while phenyl-, benzyl-, and (4-methoxyphenyl)hydrazine reacted effectively without catalyst in refluxing xylene.

Journal Article↗
PubMed1980

Intoxication with pyrazolones.

1 About 50 severe or fatal (mostly accidental) cases of intoxication in children by pyrazolones have been reported in the German literature of the past 59 years. 2 Characteristic symptoms are impaired consciousness progressing to coma and convulsions. In addition, sudden apnoea and cardiac arrest may occur. Hepatic lesions may develop after a latent period of 12-24 hours. 3 Haemoperfusion seems to be the only therapeutic measure which is able to reduce the total body load of all pyrazolones to a toxicologically relevant extent. Actual clinico-toxicological data from poisoned patients are not available as yet; however, distribution volumes, plasma half-lives and endogenous plasma clearances as well as removal kinetics in vitro of aminophenazone (aminopyrine), propyphenazone, metamizole (dipyrone), phenylbutazone and oxyphenbutazone as point to the efficacy of haemoperfusion with amberlite XAD-4 resin.

Aminopyrine↗