Disposition and metabolism of 3-(3-chlorophenoxy)-N-methylpyrrolidine [14C]-carboxamide in the rat, dog, and man.
Studies with a 14C-labeled sample have shown that the title compound A is readily absorbed and very rapidly excreted by the rat, dog, and man. The metabolites result from aromatic ring hydroxylation, oxidation, and dealkylation of the urea methyl group, and oxidative ring opening of the pyrrolidine ring. Rat metabolites were 3-(3-chloro-4-hydroxyphenoxy)-N-methyl-l-pyrrolidinecarboxamide (C) 3-(3-chloro-4-hydroxyphenoxy)-1-pyrrolidinecarboxamide (D), 3-(3-chlorohydroxyphenoxy)-1-pyrrolidinecarboxamide (E), 3-(3-chlorophenoxy)-4([(methylamino)-carbonyl]amino)butanoic acid (G), 3-(3-chlorophenoxy)-4[(aminocarbonyl)amino]butanoic acid (H). Dog metabolites were C, D, G, and H. Human metabolites were 3-(3-chloro-4-hydroxyphenoxy)-N-formyl-l-pyrrolidinecarboxamide (F), C, D, G, and H. An electron-capture gas chromatographic assay for the parent compound is described. Whole-body autoradiograms of rat slices and the tissue residue data from these slices are reported and indicate rapid tissue depletion of radioactivity.
D000818:Animals; D002219:Carbamates / Q000097:blood / Q000378:metabolism / Q000652:urine; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D004285:Dogs; D005965:Glucuronates / Q000652:urine; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D009928:Organ Specificity; D011759:Pyrrolidines / Q000097:blood / Q000378:metabolism* / Q000652:urine; D051381:Rats; D013045:Species Specificity; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D013997:Time Factors
D002219:Carbamates; D005965:Glucuronates; D011759:Pyrrolidines