Detail of "17617-60-6"

Reference

In vitro and ex vivo inhibition by flutoprazepam of [3H]flunitrazepam binding to mouse brain receptors

In vitro and ex vivo inhibition by flutoprazepam of [3H]flunitrazepam binding to mouse brain receptors. Oki, K.; Sukamoto, T.; Ito, K.; Nose, T. (Pharm. Res. Cent., Kanebo Ltd. Co., Osaka 534, Japan). Arch. Int. Pharmacodyn. Ther., 269(2), 180-6 (English) 1984. CODEN: AIPTAK. ISSN: 0003-9780. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The ability of flutoprazepam (I) [25967-29-7], a new antianxiety drug of the benzodiazepine class, to inhibit [3H]flunitrazepam binding to mouse brain receptors was investigated in vitro and ex vivo (measurement of [3H]flunitrazepam binding in vitro after in vivo treatment of animals with unlabeled drugs). The Ki values for [3H]flunitrazepam binding in vitro were as follows: flutoprazepam (13.0 nM), diazepam [439-14-5] (2.7 nM), nitrazepam [146-22-5] (5.3 nM), prazepam [2955-38-6] (68.5 nM) and chlordiazepoxide [58-25-3] (234 nM). Two metabolites of flutoprazepam, N-desalkylflutoprazepam [2886-65-9] (Ki = 1.2 nM) and N-desalkyl-3-OH-flutoprazepam [17617-60-6] (Ki = 3.1 nM) also inhibited [3H]flunitrazepam binding in vitro with higher potencies than that of flutoprazepam. Flutoprazepam was found to be more active in inhibiting [3H]flunitrazepam binding ex vivo and in preventing pentetrazole convulsions than predicted from Ki values. The ID50 values for inhibiting [3H]flunitrazepam binding ex vivo were 0.32 mg/kg, orally (flutoprazepam), 0.89 mg/kg, orally (diazepam), 0.94 mg/kg, orally (nitrazepam), 1.98 mg/kg, orally (prazepam) and 23.3 mg/kg, orally (chlordiazepoxide), resp. The correlation between ID50 values ex vivo and ED50 values for preventing pentetrazole convulsions was highly significant. It appears that flutoprazepam can exert its pharmacol. activities by itself, and the 2 metabolites also play an important role in the effects of flutoprazepam in vivo.

The disposition and metabolism of a hypnotic benzodiazepine, quazepam, in the hamster and mouse

The disposition and metabolism of a hypnotic benzodiazepine, quazepam, in the hamster and mouse. Hilbert, James; Pramanik, Birendra; Symchowicz, Samson; Zampaglione, Nicola (Dep. Drug Metab. Pharmacokinet., Schering-Plough Corp., Bloomfield, NJ 07003, USA). Drug Metab. Dispos., 12(4), 452-9 (English) 1984. CODEN: DMDSAI. ISSN: 0090-9556. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The disposition of 14C-labeled quazepam (I) [36735-22-5] was studied in hamsters and mice after i.v. and oral dosing. In both species, I was rapidly absorbed, as indicated by the plasma Cmax being reached within 1 h of an oral dose (5 mg/kg). Also, radioactivity is essentially completely absorbed in both species, since the percentage of dose excreted in the urine was not dependent on the route of drug administration. Radioactivity was widely distributed in the tissues of both species; however, it was concd. (relative to plasma) only in the liver and kidneys. In hamsters, 66-77% of the radioactivity was excreted within 48 h, and 97% within 7 days of dosing (57% found in urine and 40% in feces after i.v. dosing; 54% in urine and 43% in feces after oral dosing). In mice, 86-88% of the radioactivity was excreted within 24 h and 98% within 4 days of dosing (43% in urine and 56% in feces after i.v. dosing; 37% in urine and 61% in feces after oral dosing). In both species, plasma levels of I accounted for a very small percentage of plasma radioactivity and the elimination half-life was short (2.4 h in hamster and 1.2 h in mice), indicating extensive 1st pass metab. for this drug. 3-Hydroxy-N-desalkyl-2-oxoquazepam [17617-60-6], 3-hydroxy-2-oxoquazepam [87075-15-8], N-desalkyl-2-oxoquazepam [2886-65-9], and 2-oxoquazepam [49606-44-2] were identified as in the main urinary and blood metabolites. Quant. but not qual. differences between the 2 species were obsd. in quazepam metab.