Costagli C, Galli A
Dipartimento Di Farmacologia Preclinica E Clinica, Università Di Firenze, Florence, Italy.
Biochem Pharmacol. 1998 May 15;55(10):1733-7. doi: 10.1016/s0006-2952(97)00676-x.
The potency of a series of anticholinesterase (anti-ChE) agents and serotonin-related amines as inhibitors of the aryl acylamidase (AAA) activity associated with electric eel acetylcholinesterase (AChE) (EC 3.1.1.7) and horse serum butyrylcholinesterase (BuChE) (EC 3.1.1.8) was examined and compared with the potency of the same compounds as ChE inhibitors. Neostigmine, physostigmine, BW 284C51, (+/-)-huperzine A, E2020, tacrine, edrophonium and heptyl-physostigmine were, in that order, the most potent in inhibiting eel AChE-associated AAA activity, their inhibitor constant (Ki) values being in the range 0.02-0.37 microM. The rank order of the same compounds as AChE inhibitors basically paralleled that of AAA, although they were in general stronger on AChE (Ki = 0.001-0.05). The peripheral anionic site inhibitors propidium and gallamine were inactive on AChE-associated AAA. Serotonin and its derivatives were slightly stronger on AAA (Ki = 7.5-30 microM) than on AChE (Ki = 20-140 microM). Tacrine (IC50 = 0.03 microM), diisopropylfluorophosphate (IC50 = 0.04 microM), heptyl-physostigmine (IC50 = 0.11 microM), physostigmine (IC50 = 0.15 microM) and tetra-iso-propylpyrophosphoramide (iso-OMPA) (IC50 = 0.75 microM) were the most potent in inhibiting horse serum BuChE-associated AAA activity. Serotonin and related amines were very weak on BuChE-associated AAA activity. These results indicate that the inhibitory potencies of the active site anti-ChE agents on the AAA activity associated with eel AChE and horse serum BuChE are closely correlated with their action on the respective ChE. In addition, the efficacy of tacrine, E2020, heptyl-physostigmine and (+/-)-huperzine A in the treatment of Alzheimer's disease is unlikely to be related to the action of these drugs on ChE-associated AAA.
研究了一系列抗胆碱酯酶（anti-ChE）药物和血清素相关胺类作为芳基酰胺酶（AAA）活性抑制剂的效力，该活性与电鳗乙酰胆碱酯酶（AChE）（EC 3.1.1.7）和马血清丁酰胆碱酯酶（BuChE）（EC 3.1.1.8）相关，并将这些化合物作为胆碱酯酶抑制剂的效力与之进行了比较。新斯的明、毒扁豆碱、BW 284C51、（±）-石杉碱甲、E2020、他克林、依酚氯铵和庚基毒扁豆碱按此顺序是抑制鳗鱼AChE相关AAA活性最有效的，它们的抑制常数（Ki）值在0.02 - 0.37微摩尔范围内。相同化合物作为AChE抑制剂的效力排序基本与作为AAA抑制剂的排序平行，尽管它们总体上对AChE的抑制作用更强（Ki = 0.001 - 0.05）。外周阴离子位点抑制剂碘化丙啶和加拉明对AChE相关的AAA无活性。血清素及其衍生物对AAA（Ki = 7.5 - 30微摩尔）的抑制作用比对AChE（Ki = 20 - 140微摩尔）的抑制作用稍强。他克林（IC50 = 0.03微摩尔）、二异丙基氟磷酸酯（IC50 = 0.04微摩尔）、庚基毒扁豆碱（IC50 = 0.11微摩尔）、毒扁豆碱（IC50 = 0.15微摩尔）和四异丙基焦磷酰胺（iso-OMPA）（IC50 = 0.75微摩尔）是抑制马血清BuChE相关AAA活性最有效的。血清素及相关胺类对BuChE相关AAA活性的抑制作用非常弱。这些结果表明，活性位点抗胆碱酯酶药物对鳗鱼AChE和马血清BuChE相关AAA活性的抑制效力与其对各自胆碱酯酶的作用密切相关。此外，他克林、E2020、庚基毒扁豆碱和（±）-石杉碱甲在治疗阿尔茨海默病方面的疗效不太可能与这些药物对胆碱酯酶相关AAA的作用有关。
