Atipamezole is a promising non-discriminative inhibitor against pan-CYP450 including diclofenac 4′-hydroxylation: A comparison with ABT for drug ADME optimization and mechanism study was written by Li, Zheng;Zhang, Yunxia;Gao, You;Xiang, Yanan;Zhang, Wenpeng;Lu, Chuang;Zhuang, Xiaomei. And the article was included in European Journal of Pharmaceutical Sciences in 2019.Name: 1H-Benzo[d][1,2,3]triazol-1-amine This article mentions the following:
Atipamezole is commonly used to recover animals from sedation-anesthesia induced by a2-adrenoceptor agonists. The purpose of this study is to evaluate atipamezole as a non-selective inhibitor of P 450 enzymes and compare it with ABT. Inhibition toward seven major human CYP450 isoform was determined for atipamezole and ABT in human, rat, and dog liver microsomes for the direct and time-dependent inhibition potentials. IC50 values toward human and animal CYPs without preincubation are 0.02-7.93μM and 20.9-1798μM for atipamezole and ABT, resp. The IC50 values of ABT after preincubation shift to 4.06-460μM. Atipamezole has more effective inhibition to CYP2C9 mediated diclofenac hydroxylation in human and animal liver microsomes with IC50 values of 1.50-5.20μM than that of ABT at 74.7-460μM. No IC50 shift was observed for atipamezole to CYP isoforms. In vivo utility of atipamezole was assessed by co-dosing with diclofenac in rats. At 30 mg/kg via oral, atipamezole enhanced the AUC of diclofenac by 13.1-fold and the Cmax by 5.6-fold. Similar enhancement also achieved for ABT (100 mg/kg) with AUC and Cmax increased 9.5 and 4.8-fold. As a reversible pan-CYP inhibitor, atipamezole showed less species difference than ABT. It provides a better and easier to use alternative to ABT for ADME optimization and elucidating mechanistic drug metabolism or toxicity studies. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Name: 1H-Benzo[d][1,2,3]triazol-1-amine).
1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6) belongs to triazole derivatives. Triazoles are important five-member nitrogen heterocycles involved in a wide range of industrial applications such as agrochemicals, corrosion inhibitors, dyes, optical brighteners, as well as biologically active agents. Due to the structural characteristics, both 1,2,3- and 1,2,4-triazoles are able to accommodate a broad range of substituents (electrophiles and nucleophiles) around the core structures and pave the way for the construction of diverse novel bioactive molecules.Name: 1H-Benzo[d][1,2,3]triazol-1-amine
Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics