The trans-cis isomerization of trans-4'-(2-hydroxy-3,5-dibromo-benzylamino)cyclohexanol in vivo and in vitro in different species.
Isomerization of trans-4'-(2-hydroxy-3,5-dibromo-benzylamino)cyclohexanol (HDBC) in vivo has been investigated in horse, cow, dog, rat and man. Following oral administration of 4'-trans-HDBC to the horse, a very efficient first-pass trans-cis isomerization was observed. In the urine of the horse and cow, 40% and 29% respectively of the conjugated alcohols consisted of the 4'-cis isomer. Isomerization in rat and dog took place only to a small extent, and in man no 4'-cis isomer was detected. Oxidation of HDBC to the corresponding ketone, at pH 9.0, was highest with horse- and rat-liver 10 000 g supernatants and lowest with dog-liver supernatant. Reduction of the ketone with 10 000 g liver supernatants and with cryst. horse-liver alcohol dehydrogenase led to the formation of the alcohol containing 42-69% as the 4'-cis isomer, whereas after reduction with NaBH4 the alcohol contained only 20% of the 4'-cis isomer. This indicates that the conformer with the lower energy (1' and 4' position equatorially substituted) preferentially formed only during chemical reduction. A correlation between the formation of the ketone in vitro and the formation of 4'-cis-HDBC in vivo was observed in the horse, cow and dog. No similar correlation was found in the rat, where a high in vivo trans-cis isomerization might have been expected from the in vitro data.
D000284:Administration, Oral; D000588:Amines / Q000378:metabolism*; D000818:Animals; D001596:Benzylamines / Q000378:metabolism* / Q000652:urine; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D003511:Cyclohexanols / Q000378:metabolism* / Q000652:urine; D004285:Dogs; D006736:Horses; D006801:Humans; D007536:Isomerism; D007659:Ketones / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D013045:Species Specificity
D000588:Amines; D001596:Benzylamines; D003511:Cyclohexanols; D007659:Ketones; C049653:dembrexine