In vitro and in vivo effects of some benzodiazepine drugs on human and rabbit erythrocyte carbonic anhydrase enzymes

被引:11
作者
Senturk, Murat [1 ,2 ]
Alici, Haci Ahmet [3 ]
Beydemir, Sukru [1 ,4 ]
Kufrevioglu, Omer Irfan [1 ]
机构
[1] Ataturk Univ, Fac Sci, Dept Chem, Erzurum, Turkey
[2] Ibrahim Cecen Univ Agri, Fac Sci & Arts, Dept Chem, Agri, Turkey
[3] Ataturk Univ, Fac Med, Dept Anesthesiol & Intens Care, Erzurum, Turkey
[4] Ataturk Univ, Biotechnol Res Ctr, Erzurum, Turkey
关键词
Carbonic anhydrase; benzodiazepine; midazolam; diazepam; inhibition; PHENOLIC-COMPOUNDS; MIDAZOLAM; INHIBITION; ISOZYMES; PURIFICATION; PHARMACOLOGY; RESPONSES; DIAZEPAM; METALS;
D O I
10.3109/14756366.2011.607447
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Carbonic anhydrase inhibitors (CAIs) are a class of pharmaceuticals used as antiglaucoma agents, diuretics and antiepileptics. Thus, discovery of novel CAIs has become of great importance in the recent years. In the current study, in vitro and in vivo inhibition effects of benzodiazepine drugs, diazepam and midazolam, on human erythrocytes carbonic anhydrase I and II isozymes were investigated. After purification of the isoenzymes, in vitro inhibition assays were performed and K-i values were determined to be of 141.5 mu M and 40.7 mu M for hCA I and of 5.11 mu M and 0.58 mu M against hCA II by the esterase activity assay, respectively. The drugs showed strong inhibitory effects on hCA II, in the same range as the clinically used sulphonamide acetazolamide. For in vivo studies, five adult male New Zealand White rabbits (3-4.2 kg) were selected for intravenous administrations of the drugs (2 mg/kg and 0.2 mg/kg body weight, respectively). The enzyme was significantly inhibited by 2 mg/kg diazepam (p < 0.05), and 0.2 mg/kg midazolam (p < 0.05) for up to 30 min following intravenous administration.
引用
收藏
页码:680 / 684
页数:5
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