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At least 847 records · Page 47Linked to original sources
PubMed1982

Nafazatrom (Bay g-6575), an antithrombotic and antimetastatic agent, inhibits 15-hydroxyprostaglandin dehydrogenase.

Nafazatrom (Bay g-6575) is a potent antithrombotic agent which has been suggested to stimulate prostacyclin (PGI2) release from the vascular wall. This study demonstrates that nafazatrom inhibits 15-hydroxyprostaglandin dehydrogenase (15-OH PGDH) of bovine lung and vascular wall. As 15-OH PGDH, the key prostaglandin (PG) catabolizing enzyme, inactivates PGI2 as well as PGE2 and PGF2 alpha, inhibition of this enzyme can result in increased levels of PGI2. Nafazatrom, in the micromolar range, inhibits the metabolism of PGs by 15-OH PGDH in a dose-dependent manner. The IC50 for inhibition of 15-OH PGDH was estimated to be 18.5 microM when [3H]PGF2 alpha was used as substrate. We also estimated nafazatrom-induced changes in PGI2 degradation by lung 15-OH PGDH using the more stable methyl ester (ME) of PGI2 (PGI2-ME) which resists spontaneous degradation. Nafazatrom also inhibited catabolism by 15-OH PGDH of [3H]PGI2-ME to [3H]6,15-diketo-PGF1 alpha ME. These results suggest that the inhibitory action of nafazatrom on 15-OH PGDH contributes to its antithrombotic effect by prolonging the biological half-life of PGI2.

Animals↗
PubMed1982

Protective actions of nafazatrom in traumatic shock.

3-Methyl-(1-[2-naphthyloxy]-ethyl)-2-pyrazolin-5-one (nafazatrom), a new antithrombotic agent, at doses of 0.5 to 2.0 mg/kg significantly prolonged survival of rats after induction of traumatic shock. Nafazatrom did not exert significant effects on arterial blood pressure in either control or shock animals. However, nafazatrom significantly prevented the plasma accumulation of the lysosomal protease cathepsin D and of the cardiotoxic peptide, myocardial depressant factor (MDF). In addition, nafazatrom (10 microgram/ml) significantly stabilized lysosomal membranes in isolated liver lysosomal suspensions, and inhibited proteolysis in pancreatic homogenates. Thus, nafazatrom exerts significant anti-shock activity which appears to be related to its favorable cellular and metabolic effects.

Animals↗
PubMed1982

Measurement of gastric mucosal blood flow in dogs by the 99mTc-4-methylaminophenazone clearance technique.

In anesthetized dogs, correlation was found between the 99mTc-4-methylaminophenazone and aminopyrine clearance measured in the same animal after administration of the gastric secretory stimulants vasopressin or glucagon. Similar correlation was observed between the 99mTc-4-methylaminophenazone and [14C]aminopyrine clearance during histamine administration. The clearance values were always corrected by the actual degree of dissociation of the radioactive molecules. The results suggest that 99mTc-4-methylaminophenazone is suitable to study circulatory changes in human gastric mucosa. Advantages of this compound include a much lower dose of radiation absorbed by the patient and his surroundings, a simplified measurement technique, and considerably reduced expenses.

Aminopyrine↗
PubMed1982

[Results of measuring the blood flow in the gastric mucosa of dogs by the 99mTc-4-methylaminophenazone clearance method].

In anesthetized dogs, a good correlation was found between the [99mTc]-4-methylaminophenazone and aminopyrine clearances measured in the same animal after administration of gastric secretory stimulants vasopressin or glucagon. A similarly good correlation was observed between the [99mTc]-4-methylaminophenazone and [14C]-aminopyrine clearance during histamine administration. The clearance values were always corrected by the actual degree of dissociation of the radioactive molecules. The results suggest that [99mTc]-4-methylaminophenazone is suitable for the study of the circulatory changes in human gastric mucosa. It has the advantages of a much lower absorbed dose of radiation for the patient and his surroundings, a simplified measurement technique and considerably reduced expenses.

Aminopyrine↗
PubMed1981

[Optimization of the composition of a multicomponent drug form by mathematical investigational designing and experimental testing (author's transl)].

Experiments have been performed to optimize the composition of tablets with 250 mg of noramidopyrine methanesulphonate sodium, 250 mg of aminophenazone and 100 mg of caffeine + sodium benzoate. The effects of the adjuvants Micricell, Aerosil 200, Kollidon CE 5050 and wheat starch on different tablet characteristics (disintegration, mechanical strength, friability and rheological properties) were studied. The results obtained permitted to prepare tablets with good properties: disintegration time, up to 194 s; mechanical strength, greater than 12 kg; friability, less than 0.250%.

Aminopyrine↗
PubMed1981

[Quantitative thin-layer chromatographic estimation of aminophenazone (I.N.N.), 4-methylaminophenazone and 4-aminophenazone in plasma (author's transl)].

A TLC method for measurement of aminophenazone (1) and of its degradation products 4-methylaminophenazone (2) and 4-aminophenazone (3) in plasma was described. After chloroform extraction amd separation on Silufol plates the substances were stained by ferric chloride/potassium hexacyanotoferrate(III) and the area of the spots was measured. Concentrations from 1 to 25 micrograms 1, 2 and 3 per ml plasma could be estimated.

Aminopyrine↗
PubMed1995

Potential cardiotoxicity with the use of DuP-941: a case report.

OBJECTIVE: To describe the clinical and pathological features of a patient with probable cardiotoxicity related to a newer chemotherapeutic agent, DuP-941. PATIENT AND METHODS: A 42-year-old woman with metastatic breast carcinoma treated with only DuP-941 developed, and died of, heart failure for which no other explanation was apparent. RESULTS: Clinically the patient's heart failure resembled that associated with anthracycline cardiotoxicity, as did the pathological features seen at autopsy. CONCLUSION: DuP-941 is a new chemotherapeutic drug that may supplant some uses of the anthracyclines because the former may have less cardiotoxicity. This report suggests that in some cases DuP-941 may have cardiotoxic effects as well.

Adult↗
PubMedDate not supplied

Detection and identification of human urinary metabolites of biantrazole (CI-941).

The anthrapyrazole derivative biantrazole (7-hydroxy-2-[2-[(2-hydroxyethyl)amino]ethyl]-5-[[2-[(2- hydroxyethyl)amino]ethyl]amino]-anthra[1,9-cd]pyrazol-6(2H)-one dihydrochloride, CI-941) is currently under clinical investigation for the treatment of breast cancer. Up to now, pharmacokinetic data of the drug were acquired using an HPLC assay lacking the capability to detect and separate metabolites of CI-941. Therefore an HPLC separation procedure was developed that is compatible with the ionization methods used most frequently for coupling to mass spectrometry. Application of the HPLC analysis to the urine of a patient treated with biantrazole clearly demonstrated the presence of two more polar metabolites. The molecular masses of the metabolites were determined during an HPLC-MS coupling with ionspray ionization after injection of an extract of only 15 ml of patient urine. Both metabolites have the same UV-VIS spectra as biantrazole and exhibit collision-induced mass spectra typical for aminoalkylamino-substituted anthrapyrazoles. The daughter ion mass spectra acquired during the HPLC separation allowed the identification of the chemical structures of both metabolites. Metabolite 1 was identified as the oxidation product of CI-941 with both side chains oxidized at the hydroxymethylene groups to the corresponding dicarboxylic acid derivative, whereas metabolite 2 was shown to be the analogous monooxidation product. However, the unsymmetrical molecular structure of CI-941 did not allow us to distinguish between two possible isomers of metabolite 2. Quantitation of the drug and its metabolites in patient urine collected during a time period of 100 hr showed that 0.55% of the dose were excreted as metabolite 1, 0.34% of the dose as metabolite 2, and 7.8% of the dose as unchanged drug.

Anthraquinones↗
PubMed1994

Anti-inflammatory properties of 3-methylpyrazolin-5-(4 H)-one-4-[3'-methoxy-4' (2'',3'',4'',6''-tetra-O-acetyl-beta-D-glycopyranosyl]benzylidene (compound IIIA).

Oral treatment of compound IIIA exhibited dose related inhibitory action in acute tests of carrageenan, histamine and dextran-induced oedema in rats. Marked inhibitory action of the compound was found when it was administered intraperitoneally in animals. It displayed prominent anti-arthritic activity in chronic tests of adjuvant and formaldehyde-induced arthritis in rats. It prevented the arthritis associated rise in total leucocyte count and erythrocyte sedimentation rate. It also lowered the levels of exudate volume and migration of leucocytes in carrageenan induced pleurisy in rats. It did not exhibit any analgesic, antipyretic or ulcerogenic effect. No mortality was recorded up to 2 g/kg in mice on oral or intraperitoneal treatment over a period of 72 hr.

Animals↗
PubMed1993

Validity of saliva samples for the estimation of dipyrone metabolites pharmacokinetics.

Plasma and saliva pharmacokinetics of dipyrone (CAS 5907-38-0) metabolites, 4-methylaminoantipyrine (MAA), 4-aminoantipyrine (AA), 4-formylaminoantipyrine (FAA) and 4-acetylaminoantipyrine (AAA), has been studied in 10 healthy volunteers, after oral administration of 1.0 g dipyrone, MAA, AA, FAA and AAA saliva concentrations correlated significantly with the respective plasma concentrations (r = 0.81, r = 0.62, r = 0.83 and r = 0.91, p < 0.001). MAA and AA concentrations in saliva were lower than in plasma while the FAA and AAA saliva concentrations were similar to the respective plasma concentrations. The saliva/plasma concentration ratios were highly dependent on sampling time. The elimination half-life of the final metabolites FAA and AAA can be equally evaluated from plasma and saliva data. For MAA, plasma and saliva t1/2 values were significantly correlated despite a substantial intra-subject difference. No correlation was found for AA plasma and saliva derived pharmacokinetic parameters. Similar to the plasma AAA/AA ratio, the saliva AAA/AA ratio in spot sample 6 h following oral dose might be proven to be a reliable discriminatory index for acetylation phenotyping.

Acetylation↗
PubMed1993

[Ergotamine-induced rectal stenosis in a patient with long-term migraine].

A 36 year old woman was admitted to our hospital for treatment of a high-grade rectal stenosis of unknown origin. She had a history of migraine going back 10 years. On intensive questioning she admitted using up to 5 ergotamine-containing suppositories a day. On the basis of history and clinical investigations the rectal stenosis must be connected with the abuse of ergotamine-containing suppositories. This case demonstrates that patients with an unexplained rectal syndrome should be asked for analgetics-containing suppositories specifically. Only discontinuation of treatment in time can preserve the patient from development of a rectal stenosis. In case of a rectal stenosis surgical treatment can be avoided by means of endoscopic controlled dilatation.

Adult↗
PubMed1995

Lack of interaction between zidovudine and 4-methyl-amino-antipyrine, the active metabolite of metamizole, in human liver in vitro.

Zidovudine (AZT) is eliminated by extensive metabolism to an ether glucuronide (GAZT). The nonnarcotic analgesic metamizole (dipyrone) is a typical polydrug, the active metabolite being 4-methyl-amino-antipyrine (4-MAA). About 20% of 4-MAA is excreted in the form of glucuronide in the urine. The aim of this study was to investigate whether 4-MAA inhibits the glucuronidation of AZT, by comparing the GAZT formed in the presence and absence of 4-MAA in the microsomal fractions. Microsomal fractions were obtained from 6 human livers. AZT and 4-MAA were added in concentrations of 1 mmole, corresponding to the therapeutically relevant plasma concentrations of both drugs. Incubation time was 20 min. Concentrations of GAZT were measured using reverse-phase HPLC (high performance liquid chromatography). The mean value of GAZT formed in the microsomal samples without the addition of 4-MAA was 1.87 +/- 0.74 pmole/mg protein. In the presence of 4-MAA, the concentrations averaged 1.77 +/- 0.77 pmole/mg protein, and did not differ significantly from those measured without 4-MAA. In conclusion, the glucuronidation of AZT is not inhibited by 4-MAA, the main active metabolite of metamizole. From the in vitro findings it is predicted that concomitant metamizole administration may fail to enhance by metabolic interference the AZT concentrations under therapy.

Antiviral Agents↗