The relationship between oxime-induced reactivation of carbamylated acetylcholinesterase and antidotal efficacy against carbamate intoxication.

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  • Author(s): Harris LW;Harris LW; Talbot BG; Lennox WJ; Anderson DR
  • Source:
    Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 1989 Mar 15; Vol. 98 (1), pp. 128-33.
  • Publication Type:
    Comparative Study; Journal Article
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Academic Press Country of Publication: United States NLM ID: 0416575 Publication Model: Print Cited Medium: Print ISSN: 0041-008X (Print) Linking ISSN: 0041008X NLM ISO Abbreviation: Toxicol Appl Pharmacol Subsets: MEDLINE
    • Publication Information:
      Publication: New York, NY : Academic Press
      Original Publication: New York.
    • Subject Terms:
      Acetylcholinesterase/*blood ; Atropine/*pharmacology ; Carbaryl/*toxicity ; Cholinesterase Reactivators/*pharmacology ; Erythrocytes/*enzymology ; Physostigmine/*toxicity ; Pralidoxime Compounds/*pharmacology ; Pyridinium Compounds/*pharmacology; Animals ; Antidotes/pharmacology ; Cholinesterase Inhibitors/blood ; Drug Interactions ; Lethal Dose 50 ; Male ; Oximes ; Rats ; Rats, Inbred Strains
    • Abstract:
      The efficacy of the oximes pyridinium-2-aldoxime methochloride (2-PAM) and 1-[[[(4-aminocarbonyl)pyridinio]methoxy]methyl]-2-[(hydro xyimino) methyl]pyridinium dichloride (HI-6), in combination with atropine (At), against lethality by either carbaryl (CA) or physostigmine (Phy) was investigated in rats. The protection by At, 8 mg/kg, iv, against CA intoxication was reduced by 2-PAM (22 mg/kg, iv) and HI-6 (50 mg/kg, iv) from a protective ratio (PR) of 6.6 to 3.5 and 2.3, respectively. However, in Phy-intoxicated rats, the administration, iv, of At alone, At + 2-PAM, or At + HI-6 at 1 min following Phy provided good protection and resulted in PRs of 7.2, 8.8, and 23.3, respectively. In experiments on decarbamylation of inhibited acetylcholinesterase (AChE), HI-6 and 2-PAM accelerated (p less than 0.05) the decarbamylation of Phy-inhibited AChE in vitro, and HI-6 decreased (p less than 0.05) the inhibition of whole blood AChE in Phy-intoxicated rats. These findings show that the protection was increased substantially by the use of either 2-PAM or HI-6 against Phy-induced lethality, whereas the use of oximes against carbaryl poisoning was contraindicated. Furthermore, even though CA and Phy are both N-methyl carbamates, the data indicate that there is no adverse interaction between 2-PAM or HI-6 and Phy.
    • Accession Number:
      0 (Antidotes)
      0 (Cholinesterase Inhibitors)
      0 (Cholinesterase Reactivators)
      0 (Oximes)
      0 (Pralidoxime Compounds)
      0 (Pyridinium Compounds)
      7C0697DR9I (Atropine)
      9U1VM840SP (Physostigmine)
      EC 3.1.1.7 (Acetylcholinesterase)
      HUV88P6SJS (asoxime chloride)
      P7MU9UTP52 (pralidoxime)
      R890C8J3N1 (Carbaryl)
    • Publication Date:
      Date Created: 19890315 Date Completed: 19890502 Latest Revision: 20190727
    • Publication Date:
      20231215
    • Accession Number:
      10.1016/0041-008x(89)90140-3
    • Accession Number:
      2494778