Comparative Metabolic Study of Nimetazepam and its Desmethyl Derivative (Nitrazepam) in Rats

Yanagi, Yoshikazu; Haga, Fumie; Endo, Masao; Kitagawa, Sumio

doi:10.3109/00498257509052071

Cited by 16 publications

(3 citation statements)

References 9 publications

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“…In 2008, another team at Bayer presented an interesting mix and match approach involving the jasmonate structure and the active metabolite of the 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibiting herbicide isoflutole (Figure ). By combining the diketonitrile motif of active metabolite 98 with jasmonic acid ( 2 ), the hybrid herbicide 99 was furnished. Additional HPPD motifs were also incorporated, such as the cyclohexyl triketone motif, , thus affording the new hybrid structure 100 .…”

Section: Jasmonic Acidmentioning

confidence: 99%

Inspired by Nature: Isostere Concepts in Plant Hormone Chemistry

Frackenpohl

Abel

Alnafta

et al. 2023

J. Agric. Food Chem.

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Chemical concepts such as isosteres and scaffold hopping have proven to be powerful tools in agrochemical innovation processes. They offer opportunities to modify known molecular lead structures with the aim to improve a range of parameters, including biological efficacy and spectrum, physicochemical properties, stability, and toxicity. While recent biochemical insights into plant-specific receptors and signaling pathways trigger the discovery of the first lead structures, the disclosure of such a new chemical structure sparks a broad range of synthesis activities giving rise to diverse chemical innovation and often a considerable boost in biological activity. Herein, recent examples of isostere concepts in plant-hormone chemistry will be discussed, outlining how synthetic creativity can broaden the scope of natural product chemistry and giving rise to new opportunities in research fields such as abiotic stress tolerance and growth promotion.

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Section: Jasmonic Acidmentioning

confidence: 99%

Inspired by Nature: Isostere Concepts in Plant Hormone Chemistry

Frackenpohl

Abel

Alnafta

et al. 2023

J. Agric. Food Chem.

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“…The protective effect is explained by the expansion and fluidization of the membrane (Seeman, 1972). Figure 1 demonstrates that benzyl alcohol readily antagonises the effect of lignocaine; the effect of lignocaine (5 mM Lignocaine (mM) Figure 1 The effects of lignocaine on hypotonic haemolysis in the absence (0) and presence (0) Nitroreduction is an important route of metabolism for nitrazepam (1,3-dihydro-7-nitro-5-phenyl-2H-1,4-benzodiazepine-2-one) in rat and man (Yanagi, Haga, Endo & Kitagawa, 1975;Beyer & Sadee, 1969). Since the intestinal flora appear to play a major role in the nitroreduction of p-nitrobenzoic acid and p-nitrobenzenesulphonamide (Wheeler, Soderberg & Goldman, 1975) I.Ci/kg), and water orally (25 ml/kg).…”

mentioning

confidence: 99%

“…Three weeks later, the experiment was repeated with the 'contaminated' rats. After measuring total radioactivity in the urine and faeces, urinary radioactivity was examined further by extracting it from the alkalinized urine with butan-l-ol and chromatographing the extract (Yanagi et al, 1975).…”

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confidence: 99%

PROCEEDINGS OF THE British Pharmacological Society

1978

British J Pharmacology

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Involvement of the intestinal microflora in nitrazepam‐induced teratogenicity in rats and its relationship to nitroreduction

Takeno

Sakai

1991

Teratology

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A study was undertaken to investigate the relationship between nitroreduction of nitrazepam and its teratogenic effects and the involvement of the intestinal microflora in Sprague-Dawley rats. Incubation of bacterial suspensions from rat cecal contents with nitrazepam resulted in extensive reduction to 7-aminonitrazepam. Rat liver homogenates also reduced nitrazepam but only under anaerobic conditions. Following oral administration of 300 mg/kg nitrazepam to pregnant rats, total excretion of reduced metabolites (7-aminonitrazepam and 7-acetylaminonitrazepam) in urine and feces accounted for approximately 30% of the administered dose. When antibiotics were administered to dams to deplete their intestinal microflora prior to administration to nitrazepam, the total excretion of the reduced metabolites in the urine and feces decreased to 2% of the dose. Nitroreductase activity of cecal contents was almost completely suppressed by antibiotic pretreatment, but the activity of liver homogenates was not significantly altered by the same treatment. The incidence of nitrazepam-induced malformations was markedly decreased by antibiotic pretreatment. These results suggest that the intestinal microflora plays an important role in the reductive metabolism of nitrazepam and that the teratogenicity of nitrazepam may be related to its nitroreduction by the microflora.

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Comparative Metabolic Study of Nimetazepam and its Desmethyl Derivative (Nitrazepam) in Rats

Cited by 16 publications

References 9 publications

Inspired by Nature: Isostere Concepts in Plant Hormone Chemistry

Inspired by Nature: Isostere Concepts in Plant Hormone Chemistry

PROCEEDINGS OF THE British Pharmacological Society

Involvement of the intestinal microflora in nitrazepam‐induced teratogenicity in rats and its relationship to nitroreduction

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