Hydrolysis of an acetylthiocholine by pralidoxime iodide (2-PAM)

被引:30
|
作者
Sakurada, Koichi [1 ]
Ikegaya, Hiroshi [1 ]
Ohta, Hikoto [1 ]
Akutsu, Tomoko [1 ]
Takatori, Takehiko [1 ]
机构
[1] Natl Res Inst Police Sci, Kashiwa, Chiba 2770882, Japan
基金
日本学术振兴会;
关键词
2-PAM; AChE; ASCh; ACh; VX;
D O I
10.1016/j.toxlet.2006.07.339
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Pralidoxime iodide (2-PAM), an antidote approved for the reactivation of inhibited acetylcholinesterase (AChE) in organophosphate poisoning, dose-dependently hydrolyzed an acetylthiocholine iodide (ASCh). The AChE (0.3 U) activity inhibited by VX analog (ENMP, 0.1 mu M) increased to approximately 200% of normal levels after a dosage of 5 mM 2-PAM (control 0.132 +/- 0.012 U/ml, 5 mM 0.253 +/- 0.026 U/ml). This result indicates that 2-PAM produced a thiocholine from the ASCh by hydrolysis. High-performance liquid chromatography (HPLC) analysis was then performed to further clarify the hydrolysis of ASCh with 2-PAM. It was clear that 2-PAM was converted to acetylated 2-PAM with acetic acid produced from ASCh by hydrolysis. Next, we tried to compare this esterase-like activity of 2-PAM with that of obidoxime, which is known as a strong reactivator of inhibited AChE, and with diacetylmonoxime, known as a weak reactivator. All of these oximes showed esterase-like activity, and their strengths were consistent with those of known reactivators of inhibited AChE. These results indicate that a great deal of the data obtained previously with ASCh relating to the effects of oximes must be rechecked. It is clear that oximes easily hydrolyze ASCh. We therefore strongly caution that the method of determining AChE activity with ASCh is not suitable for examining the effects of oximes. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:255 / 260
页数:6
相关论文
共 50 条
  • [41] THE EFFECT OF 2-FORMYL-1-METHYLPYRIDINIUM IODIDE OXIME (2-PAM) ON REACTIVATION OF TISSUE CHOLINESTERASE FOLLOWING POISONING BY A CERTAIN PHOSPHATE ANTICHOLINESTERASE
    OLEARY, JF
    HARRISON, B
    GROBLEWSKI, G
    WILLS, JH
    FEDERATION PROCEEDINGS, 1959, 18 (01) : 430 - 430
  • [42] SYMPATHOMIMETIC EFFECTS OF 2-PYRIDINE ALDOXIME METHYLCHLORIDE (2-PAM CL)
    ZARRO, VJ
    DIPALMA, JR
    JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 1965, 147 (02): : 153 - &
  • [43] CHOLINESTERASE INHIBITION BY PARATHION IN RHESUS MONKEYS AND LIMITED EFFECT OF 2-PAM
    SERRONE, DM
    STEIN, AA
    COULSTON, F
    EXPERIMENTAL AND MOLECULAR PATHOLOGY, 1969, 11 (01) : 99 - &
  • [44] Nonenzymatic Hydrolysis of Acetylthiocholine by Silver Nanoparticles
    Hernandez, Belen
    Sanchez-Cortes, Santiago
    Houze, Pascal
    Ghomi, Mahmoud
    JOURNAL OF PHYSICAL CHEMISTRY C, 2019, 123 (04): : 2378 - 2385
  • [45] Kinetics of hydrolysis of acetylthiocholine and acetylcholine by cholinesterases
    Komersová, A
    Komers, K
    Zdrazilová, P
    CHEMICO-BIOLOGICAL INTERACTIONS, 2005, 157 : 387 - 388
  • [46] Prolonged treatment with 2-PAM in a large amount of organophosphate insecticide intoxication
    不详
    CLINICAL TOXICOLOGY, 2005, 43 (06): : 738 - 739
  • [47] EFFECTS OF ATROPINE, 2-PAM, OR PYRIDOSTIGMINE IN EUVOLEMIC OR HEMORRHAGIC CONSCIOUS SWINE
    WADE, CE
    WARING, PP
    TRAIL, DS
    GILDENGORIN, VL
    WILLIAMS, BF
    BONNER, GD
    MILITARY MEDICINE, 1988, 153 (09) : 470 - 476
  • [48] Pralidoxime hydrolysis of thiocholine esters
    Pannbacker, RG
    Oehme, FW
    VETERINARY AND HUMAN TOXICOLOGY, 2003, 45 (01) : 39 - 40
  • [49] Pralidoxime hydrolysis of thiocholine esters
    Petroianu, G
    Maleck, W
    VETERINARY AND HUMAN TOXICOLOGY, 2003, 45 (03) : 166 - 167
  • [50] INFLUENCE OF OXIMES ON ACETYLTHIOCHOLINE HYDROLYSIS RATE
    KARLOG, O
    HOPFNERP.HE
    BIOCHEMICAL PHARMACOLOGY, 1963, 12 (06) : 590 - &