Brien J F, Tam G S, Cameron R J, Steenaart N A, Loomis C W
Can J Physiol Pharmacol. 1985 May;63(5):438-43. doi: 10.1139/y85-076.
Methyltetrazolethiol (1-methyl-5-mercapto-1,2,3,4-tetrazole, MTT) is a heterocyclic substituent of the cephalosporin antibiotics, cefamandole, cefoperazone, and moxalactam. Pretreatment of rats with MTT has been reported to increase blood acetaldehyde concentration after ethanol administration. The time course of MTT-induced inhibition of hepatic aldehyde dehydrogenases (ALDH) was determined in adult, male Sprague-Dawley rats in comparison with the hepatic ALDH inhibition induced by calcium carbimide (calcium cyanamide, CC) and disulfiram (D). The apparent onset of maximal inhibition of hepatic low Km ALDH occurred at 2 h for 50 mg/kg MTT (subcutaneous, s.c.) and 7 mg/kg CC (oral) and at 24 h for 300 mg/kg D (oral). The relative magnitude of maximal inhibition of low Km ALDH was CC greater than D greater than MTT. The relative duration of enzyme inhibition was D greater than MTT greater than CC. High Km ALDH was only inhibited by CC. Hepatic low Km ALDH was selectively inhibited by s.c. and oral administration of 125 mg/kg MTT. For s.c. administration of 125 mg/kg MTT, the magnitude of maximal enzyme inhibition and the duration of inhibition were greater than for the 50 mg/kg dose. Oral administration of 125 mg/kg MTT produced similar inhibition of hepatic low Km ALDH compared with s.c. administration of the same dose. The time course of blood ethanol and acetaldehyde concentrations was determined for the intravenous infusion of two 0.3-g/kg doses of ethanol to rats that were pretreated orally with saline (1 h), MTT (125 mg/kg, 2 h), or CC (7 mg/kg, 1 h). The relative increase in blood acetaldehyde concentration compared with saline pretreatment was CC greater than MTT. The elimination of ethanol from blood was slower in the MTT- and CC-pretreated animals, and this effect was more pronounced for CC pretreatment. Overall, the data demonstrate that the characteristics of hepatic ALDH inhibition for MTT are different from those of the known ALDH inhibitors, CC and D.
甲基四氮唑硫醇（1-甲基-5-巯基-1,2,3,4-四氮唑，MTT）是头孢菌素类抗生素头孢孟多、头孢哌酮和拉氧头孢的杂环取代基。据报道，用MTT预处理大鼠后，乙醇给药后血液中乙醛浓度会升高。与由氨甲酰钙（氰胺化钙，CC）和双硫仑（D）诱导的肝醛脱氢酶（ALDH）抑制作用相比，在成年雄性Sprague-Dawley大鼠中测定了MTT诱导的肝ALDH抑制作用的时间进程。对于50mg/kg MTT（皮下注射，s.c.）和7mg/kg CC（口服），肝低Km ALDH最大抑制作用的明显起始时间为2小时；对于300mg/kg D（口服），则为24小时。低Km ALDH最大抑制作用的相对强度为CC＞D＞MTT。酶抑制的相对持续时间为D＞MTT＞CC。高Km ALDH仅被CC抑制。皮下和口服125mg/kg MTT可选择性抑制肝低Km ALDH。对于皮下注射125mg/kg MTT，最大酶抑制作用的强度和抑制持续时间均大于50mg/kg剂量。口服125mg/kg MTT与相同剂量皮下注射相比，对肝低Km ALDH产生相似的抑制作用。对经生理盐水（1小时）、MTT（125mg/kg，2小时）或CC（7mg/kg，1小时）口服预处理的大鼠静脉输注两剂0.3g/kg乙醇后，测定血液中乙醇和乙醛浓度的时间进程。与生理盐水预处理相比，血液中乙醛浓度的相对升高为CC＞MTT。MTT和CC预处理的动物体内乙醇从血液中的消除较慢，且这种作用在CC预处理时更为明显。总体而言，数据表明MTT对肝ALDH抑制作用的特征与已知的ALDH抑制剂CC和D不同。
