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Biomedical subjects

S Pfeifer

Publications and source records attributed to S Pfeifer.

At least 73 records · Page 4Linked to original sources
PubMed1986

[Biotransformation of alimemazine].

After application of alimemazine (1) 14 phenothiazine derivatives were detected in the rat urine. The structure of 9 metabolites was elucidated (TLC detection, UV, MS), which are hydroxy, N-dealkyl, S-oxide, and sulfone derivatives of 1. The hydroxy compounds, which are the main metabolites (greater than 50%), are partly conjugated. 5-10% of sulfones were observed. Some of the metabolites were detected in the feces, too. The relationship of the excretion products in urine and feces is 75:25%.

Animals↗
PubMed1985

[Biotransformation of Chlorphenethazin (Elroquil, Marophen)].

After application of chlorophenethazine more than 20 metabolites were detected in rat urine. The structure of 14 metabolites were elucidated (UV, MS), which are hydroxy, N-dealkyl, S-oxide, sulfone and N-oxid derivatives. The hydroxy derivatives are partly conjugated. The relative high content of the sulfone of 2-chlorophenothiazine-N-acetic acid (upto 10% of the total metabolite content) is remarkable. Main metabolites are the S-oxide of the N-dealkyl derivative and 7-hydroxy-1.

Animals↗
PubMed1985

[Metabolic interactions of denaverine].

Owing to enzyme induction, the pretreatment of female Wistar rats with denaverine (Spasmalgan) produces a dose-dependent shortening of the hexobarbital sleeping time, corresponding with an increase in aminophenazon-N- and p-nitroanisol-O-demethylation, cytochrome P-450 concentration and NADPH-cytochrome-c-reductase activity in the 9000 g supernatant of liver homogenates and the relative liver weight, but no change in p-nitrophenetol-O-dealkylation and p-nitrophenol-glucuronidation. Our data suggest that denaverine is a phenobarbital-type microsomal enzyme inducer and justify the expectation of drug interactions in case of repeated application of denaverine in the framework of a combined therapy.

Animals↗
PubMed1985

[Photochemical reactivity of methaqualone-1-oxide].

The photoreactivity of methaqualone-1-oxide a main metabolite of the hypnotic methaqualone has been studied in polar and apolar solvents using UV- and daylight. Five photoproducts were isolated and identified by their analytical behaviour (TLC, UV, IR, high-resolution MS). The structure of the compounds 4, 6, 7, and 8 refer to unstable, reactive intermediates (oxaziridine, biradical) during the photolysis.

Chromatography, Thin Layer↗
PubMed1984

[Metabolic drug-drug interactions of chlorphenethiazine and chlorpromazine].

Owing to enzyme induction, the pretreatment of female Wistar rats with chlorphenethazine (Marophen, Elroquil) causes a shortening of the hexobarbital sleeping time and an increase in aminophenazone-N-, codeine phosphate-O- and p-nitroanisole-O-demethylation, a slight stimulation of p-nitrophenol-glucuronidation, but no change in aniline hydroxylation in the 9000-g-supernatant of liver homogenates. Comparative studies with chlorpromazine (Propaphenin) showed almost identical inductive activities which were in both cases inferior to that of phenobarbital. Consequently, the occurrence of drug-drug interactions of chlorphenethazine and chlorpromazine cannot be excluded in the framework of combined therapy.

Animals↗
PubMed1983

Avian acute leukemia virus OK 10: analysis of its myc oncogene by molecular cloning.

Several DNAs representing the genome of the avian acute leukemia virus OK 10 were isolated by molecular cloning from a transformed quail cell line, 9C, which contained at least six OK 10 proviruses. Recombinant lambda phages harboring the OK 10 genome and additional flanking cellular DNA sequences were studied by restriction endonuclease mapping and hybridization to viral cDNA probes. Six of the clones represented complete proviruses with similar, if not identical, viral sequences integrated at different positions in the host DNA. The organization of the OK 10 genome was determined by electron-microscopic analysis of heteroduplexes formed between the cloned OK 10 DNA and DNAs representing the c-myc gene and the genomes of two other avian retroviruses, Rous-associated virus-1 and MC29. The results indicated that the OK 10 proviral DNA is about 7.5 kilobases in size with the following structure: 5'-LTR-gag-delta polmyc-delta env-LTR-3', where LTR indicates a long terminal repeat. The oncogene of OK 10, v-mycOK 10, forms a continuous DNA segment of around 1.7 kilobases between pol and env. It is similar in structure and length to the v-myc gene of MC29, as demonstrated by restriction endonuclease and heteroduplex analyses. Two of the OK 10 proviruses were tested in transfection experiments: both DNAs gave rise to virus with the transforming capacities of OK 10 when Rous-associated virus-1 was used to provide helper virus functions.

Animals↗
PubMed1983

[Metabolic interactions of propyphenazone].

Pretreatment of female Wistar rats with propyphenazone produces a slight shortening of the hexobarbital sleeping time, and high doses of this drug cause a small increase in the relative liver weight, but there occurs no significant change in the N-demethylation of aminophenazone, the O-demethylation of codeine phosphate, the hydroxylation of aniline, the glucuronidation of p-nitrophenol, the cytochrome P-450 concentration and the NADPH-cytochrome c reductase activity in the 9.000 supernatant of liver homogenates. The differences between these properties of propyphenazone and those of aminophenazone and phenazone are discussed with reference to partition coefficients and biotransformation. The findings obtained do not justify the expectation of metabolic drug-drug interactions in case of repeated application of propyphenazone in the framework of a combined therapy.

Animals↗
PubMed1983

[Biotransformation and pharmacokinetics of (3,4-dichloroanilino)phenylacetonitrile (H 74)].

On studying the biotransformation of the potential spasmolysant (3,4-dichloroanilino)phenyl-acetonitrile (1; H 74), the authors isolated and identified (TLC, UV, high-resolution MS) from the urine and/or the faeces of male Wistar rats, apart from 1 (greater amounts only in the faeces because of incomplete oral absorption), 7 degradation products. In this connexion, the excretion of greater amounts of 3,4-dichloroaniline (2) and the detection of an accumulation of 2 in the serum in case of long-term treatment are above all disquieting from a toxicological point of view. According to extremely poor water solubility associated with high lipophilicity, the gastrointestinal absorption of 1 extends over a relatively long period of time, is incomplete and not proportional to the dose applied. Using a gas chromatographic technique, the authors found almost dose-proportional serum levels of (3,4-dichlorophenylimino)benzaldehyde (4) after oral application of 1, which is attributable to a first-pass effect (after intravenous application, below the limit of detection). 1 is subject to intensive distribution (marked alpha phase; high Vd) and its elimination is relatively slow (slow back flow from deep compartments; high reabsorption). In contrast to this, the elimination of 4 is considerably more rapid.

Acetonitriles↗
PubMed1982

Subgenomic mRNA in OK10 defective leukemia virus-transformed cells.

OK10, a defective leukemia virus, is produced as a defective particle by so-called nonproducer transformed quail fibroblasts. OK10 defective viral particles contain an 8-kilobases (kb)-long genomic RNA, lack any detectable reverse transcriptase activity, and are not infectious. We studied the genetic content of OK10 RNA extracted from both virions and infected cells. As shown by RNA-cDNA hybridizations in stringent conditions, about 77% (6.4 kb) of the OK10 8.0kb RNA was related to avian leukosis viruses in the three structural genes gag, pol, and env, as well as in the c region. The remainder of the OK10 genome-encoding capacity (</=1.6 kb) was homologous to the MC29-specific transforming sequence myc(m) and therefore has been named myc(o). EcoRI restriction analysis of the OK10 integrated proviral DNA with different probes indicated the presence of only one provirus in the OK10 QB5 clone, which agreed with the gene order: 5'-gag-Deltapol-myc(o)-Deltaenv-c- 3'. Heteroduplex molecules formed between the viral OK10 8.0-kb RNA and the 6.8-kb SacI DNA fragment of the Prague A strain of Rous sarcoma virus confirmed that structure and indicated that the myc(o) sequence formed a continuous RNA stretch of 1.4 to 1.6 kb long between Deltapol and Deltaenv. We also examined the myc(o)-containing mRNA's transcribed in OK10-transformed cells. OK10-transformed quail fibroblasts (OK10 QB5) transcribed two mRNA species of 8.0 and 3.6 kb containing the myc(o) sequence. The genetic content of the 3.6-kb species made it a possible maturation product of the genome size 8-kb species by splicing out the gag and pol sequences. In OK10-transformed bone marrow cells (OK10 BM), a stable bone marrow-derived cell line producing OK10, the myc(o) sequence was found in four RNA species of 11.0, 8.0, 7.0, and 3.6 kb. Again, the genetic content of these mRNA's indicated that (i) the 3.6-kb species could be spliced out of the 8.0-kb-genome size mRNA and (ii) the 11.0-kb-long mRNA could represent a read-through of the OK10 provirus, the corresponding maturation product being, then, a 7.0-kb mRNA. The 7.0- and 3.6- kb mRNA's both contained the myc(o) sequence, but no sequences related to the gag or pol gene. In conclusion, whereas the myc sequences have been generally thought to be expressed through a gag-onc fusion protein, as for MC29 and CMII viruses, our experiments indicate that they could also be expressed as a non-gag-related product made from a subgenomic mRNA in the OK10-transformed cells.

Animals↗