Disposition and metabolism of 1-nitropropane in rats and chimpanzees.
The metabolic fate of 1-nitropropane (1-NP) has not been previously reported. In this study male rats and chimpanzees were given single doses of 40 mg/kg ip and 5 mg/kg iv 1-[1-14C]NP, respectively. The quantitative extent of urinary and fecal elimination was similar in both species. The rats excreted 16.5% of the dose in urine and 1.7% in feces. For chimpanzees the respective values were 14.8 and 1.2%. Experiments with rats demonstrated that the major route of elimination was by exhalation. With a total elimination via the lungs of 72.6%, rats expired 10.3% of the dose as unchanged 1-NP. Five polar metabolites were isolated from the urine of chimpanzees. The two major metabolites were identified as 3-hydroxypropionic acid and N-methyl-N-2-(methylsulfinyl)ethylpropionic acid amide (NMPA). Both substances were also excreted in rat urine. The two identified metabolites indicate that 1-NP was degraded to propionic acid, part of which was modified to 3-hydroxypropionic acid or NMPA. A hypothetical pathway for the biochemical generation of NMPA is suggested.
Haas-Jobelius
M
M
Gesellschaft für Strahlen- und Umweltforschung mbH München, Institut für Okologische Chemie, Neuherberg, Federal Republic of Germany.
Korte
F
F
Coulston
F
F
D000473:Alkanes / Q000493:pharmacokinetics*; D000577:Amides / Q000378:metabolism; D000818:Animals; D002845:Chromatography; D002851:Chromatography, High Pressure Liquid; D005243:Feces / Q000032:analysis; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid / Q000031:analogs & derivatives*; D008168:Lung / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D009595:Nitroparaffins / Q000493:pharmacokinetics* / Q000652:urine; D002679:Pan troglodytes; D011407:Propane / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000652:urine; D011422:Propionates / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D000473:Alkanes; D000577:Amides; D007773:Lactates; D009595:Nitroparaffins; D011422:Propionates; C062567:N-methyl-N-2-(methylsulfinyl)ethylpropionic acid amide; D019344:Lactic Acid; C035314:1-nitropropane; C031601:hydracrylic acid; D011407:Propane