Reference

The metabolic fate of o-chloro-

The metabolic fate of o-chloro-.alpha.-(tert-butylaminomethyl)benzyl alcohol hydrochloride (C-78). III. In vitro metabolism in rat liver. Yamamoto, Yuzuru; Nitta, Keiichi; Fujihashi, Toshiaki; Uesaka, Ikuo; Nishide, Kazunori (Fac. Pharm. Sci., Kanazawa Univ., Kanazawa, Japan). Yakugaku Zasshi, 97(3), 231-6 (Japanese) 1977. CODEN: YKKZAJ. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacodynamics) Rat liver prepns. metabolized the bronchodilating agent o-chloro-.alpha.-(tert-butylaminomethyl)-benzyl alc. hydrochloride (C-78)(I) [56776-01-3] to 4-hydroxy-C-78 [58020-43-2], 3-hydroxy-C-78 [58020-41-0], 1-(o-chlorophenyl)-1,2-ethanediol [59365-60-5], and o-chloromandelic acid [10421-85-9], as in in vivo expts. Further, 2 metabolites, 5-hydroxy-C-78 [58020-39-6] and 1-(o-chlorophenyl)-2-aminoethanol [23496-56-2] were newly found in the in vitro system. However, 4-hydroxy-5-methoxy-C-78, a major metabolite in vivo, was not detected. The microsomal fraction had all the activity for forming the metabolites in the presence of NADPH-generating system. Two types of the reaction by the microsomal fraction, ring hydroxylation (major) and cleavage of the side chain (minor), were differently affected by inhibitors, and this fact suggested that they were catalyzed by different enzyme systems.

The metabolic fate of o-chloro-

The metabolic fate of o-chloro-.alpha.-(tert-butylaminomethyl)benzyl alcohol hydrochloride (C-78). II. Metabolic products in the rat. Yamamoto, Yuzuru; Higuchi, Shohei; Fujihashi, Toshiaki; Shimizu, Sakae; Nishide, Kazunori; Uesaka, Ikuo (Fac. Pharm. Sci., Kanazawa Univ., Kanazawa, Japan). Yakugaku Zasshi, 97(3), 244-50 (Japanese) 1977. CODEN: YKKZAJ. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacodynamics) The metabolic fate of o-chloro-.alpha.-(tert-butylaminomethyl)benzyl alc. hydrochloride (C 78)(I) [56776-01-3] was studied in the rat after oral administration of I-14C and the bronchodilating activities of the metabolites were also examd. The major metabolites in the urine, bile, and feces were unchanged I, 4-hydroxy- (II) [58020-43-2], 3-hydroxy- (III) [58020-41-0], and 4-hydroxy-5-methoxy-C-78 (IV) [62818-96-6], and their corresponding conjugates. As the minor metabolites, o-chlorobenzoic acid [118-91-2], o-chloromandelic acid [10421-85-9], and 1-(o-chlorophenyl)-1,2-ethanediol [59365-60-5] were detected by gas chromatog. These results suggested that the major metabolic pathway of I in the rat is hydroxylation of the benzene ring. Although IV had no activity, II had a stronger bronchodilating activity than I, and III was as effective as I, suggesting the participation of the metabolites in the bronchodilating action and durability of I.