Nielsen-Kudsk F, Jakobsen P, Magnussen I
Acta Pharmacol Toxicol (Copenh). 1980 Jul;47(1):11-6. doi: 10.1111/j.1600-0773.1980.tb02018.x.
Thymoxamine, 6-acetoxythymol-2-dimethylaminoethyl ether, is a competitive alpha-adrenoceptor blocking agent used as a vasodilator in the treatment of peripheral vascular disorders. The plasma half-life of the drug in vivo is very short. In vitro experiments showed that thymoxamine had a half-life in human plasma of about only 1 min. By using the compound as a substrate in increasing concentrations from 5-320 microgram/ml in the presence of a fixed, low concentration of plasma (0.1% v/v) at pH 7.4 and 37 degrees a hyperbolic correlation was found between the concentration of thymoxamine and the initial rate of formation of the involved reaction product, which was determined by HPLC. A linearized Michaelis-Menten plot indicated an enzymatic biotransformation. A Km-value of about 0.115 mumol ml-1 and a Vm-value of about 0.0037 mumol ml-1 min.-1 were found. Physostigmine, neostigmine and cinchocaine inhibited the biotransformation competitively. This indicated that plasma cholinesterase was the enzyme responsible. The metabolite was identified as desacetylthymoxamine by HPLC, spectrophotometry and direct inlet mass spectrometry.
百里胺，即6-乙酰氧基麝香草酚-2-二甲基氨基乙醚，是一种竞争性α-肾上腺素能受体阻断剂，用作血管扩张剂治疗外周血管疾病。该药物在体内的血浆半衰期很短。体外实验表明，百里胺在人血浆中的半衰期约仅为1分钟。在pH 7.4和37℃条件下，以固定低浓度血浆（0.1% v/v）为存在介质，将该化合物作为底物，使其浓度从5 - 320微克/毫升逐渐增加，通过高效液相色谱法测定发现，百里胺浓度与相关反应产物形成的初始速率之间呈双曲线相关性。线性化的米氏方程图表明存在酶促生物转化。测得米氏常数（Km值）约为0.115微摩尔/毫升，最大反应速率（Vm值）约为0.0037微摩尔/毫升·分钟⁻¹。毒扁豆碱、新斯的明和辛可卡因竞争性抑制这种生物转化。这表明血浆胆碱酯酶是负责该反应的酶。通过高效液相色谱法、分光光度法和直接进样质谱法鉴定该代谢产物为去乙酰百里胺。
