FarFaR - Pharmacy Repository
University of Belgrade, Faculty of Pharmacy
    • English
    • Српски
    • Српски (Serbia)
  • English 
    • English
    • Serbian (Cyrillic)
    • Serbian (Latin)
  • Login
View Item 
  •   FarFaR
  • Pharmacy
  • Radovi istraživača / Researchers’ publications
  • View Item
  •   FarFaR
  • Pharmacy
  • Radovi istraživača / Researchers’ publications
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Interaction of phosphamidon with neuropathy target esterase and acetylcholinesterase of hen brain

Authorized Users Only
1995
Authors
Jokanović, Milan
Maksimović, Matej
Stepanović-Petrović, Radica
Article (Published version)
Metadata
Show full item record
Abstract
Phosphamidon (PSM) is an organophosphorus insecticide widely used in agriculture. This study was undertaken to examine the interaction of PSM with acetylcholinesterase (AChE) and neuropathy target esterase (NTE) of hen brain in vitro and in vivo. PSM was a potent inhibitor of AChE, with an I50 of 2.9μM and second-order rate constant (ka) of 1.2×104 M-1 min-1 at 37°C. PSM-inhibited AChE aged rapidly (t1/2=1.9h). Pyridinium oximes pralidoxime, trimedoxime, obidoxime and HI-6 were effective reactivators of PSM-inhibited AChE, providing up to 75% reactivation. PSM was one of the weakest inhibitors of NTE among organophosphorus compounds, with an I50 of 19 mM and ka of 1.8 M-1 min-1 at 37°C. Inhibited NTE did not reactivate spontaneously and KF-induced reactivation was not obtained even at the earliest tested moments, so it was not clear whether aging of PSM-inhibited NTE occurred very quickly or the KF molecule could not affect the stability of phosphoryl-NTE bond. From the ratio of kas fo...r NTE and AChE (0.00015) it was predicted that delayed neuropathic effects of PSM in vivo would appear only at doses far above the acute LD50. The LD50 value of PSM p.o. for hens was 9 mg/kg. Hens were treated with a single oral dose of PSM, combined with standard antidotal treatment which included atropine, physostigmine, pralidoxime and anticonvulsant midazolam. Doses of 90 and 250 mg/kg caused up to 27% and 45% NTE inhibition 48h after poisoning, respectively. Clinical signs of neuropathy were not seen up to 25 days after treatment, which could be expected, since the proposed level (>70%) of NTE inhibition necessary for the occurrence of delayed neuropathy was not achieved. The results suggest that PSM, at doses tested, has no ability to cause delayed neuropathy in hens without showing signs of severe cholinergic intoxication.

Keywords:
Acetylcholinesterase / Neuropathy target esterase / Organophosphorus compounds / Phosphamidon
Source:
Archives of Toxicology, 1995, 69, 6, 425-428
Publisher:
  • Springer-Verlag

DOI: 10.1007/s002040050195

ISSN: 0340-5761

Scopus: 2-s2.0-0029036104
[ Google Scholar ]
10
URI
https://farfar.pharmacy.bg.ac.rs/handle/123456789/121
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Pharmacy
TY  - JOUR
AU  - Jokanović, Milan
AU  - Maksimović, Matej
AU  - Stepanović-Petrović, Radica
PY  - 1995
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/121
AB  - Phosphamidon (PSM) is an organophosphorus insecticide widely used in agriculture. This study was undertaken to examine the interaction of PSM with acetylcholinesterase (AChE) and neuropathy target esterase (NTE) of hen brain in vitro and in vivo. PSM was a potent inhibitor of AChE, with an I50 of 2.9μM and second-order rate constant (ka) of 1.2×104 M-1 min-1 at 37°C. PSM-inhibited AChE aged rapidly (t1/2=1.9h). Pyridinium oximes pralidoxime, trimedoxime, obidoxime and HI-6 were effective reactivators of PSM-inhibited AChE, providing up to 75% reactivation. PSM was one of the weakest inhibitors of NTE among organophosphorus compounds, with an I50 of 19 mM and ka of 1.8 M-1 min-1 at 37°C. Inhibited NTE did not reactivate spontaneously and KF-induced reactivation was not obtained even at the earliest tested moments, so it was not clear whether aging of PSM-inhibited NTE occurred very quickly or the KF molecule could not affect the stability of phosphoryl-NTE bond. From the ratio of kas for NTE and AChE (0.00015) it was predicted that delayed neuropathic effects of PSM in vivo would appear only at doses far above the acute LD50. The LD50 value of PSM p.o. for hens was 9 mg/kg. Hens were treated with a single oral dose of PSM, combined with standard antidotal treatment which included atropine, physostigmine, pralidoxime and anticonvulsant midazolam. Doses of 90 and 250 mg/kg caused up to 27% and 45% NTE inhibition 48h after poisoning, respectively. Clinical signs of neuropathy were not seen up to 25 days after treatment, which could be expected, since the proposed level (>70%) of NTE inhibition necessary for the occurrence of delayed neuropathy was not achieved. The results suggest that PSM, at doses tested, has no ability to cause delayed neuropathy in hens without showing signs of severe cholinergic intoxication.
PB  - Springer-Verlag
T2  - Archives of Toxicology
T1  - Interaction of phosphamidon with neuropathy target esterase and acetylcholinesterase of hen brain
VL  - 69
IS  - 6
SP  - 425
EP  - 428
DO  - 10.1007/s002040050195
ER  - 
@article{
author = "Jokanović, Milan and Maksimović, Matej and Stepanović-Petrović, Radica",
year = "1995",
abstract = "Phosphamidon (PSM) is an organophosphorus insecticide widely used in agriculture. This study was undertaken to examine the interaction of PSM with acetylcholinesterase (AChE) and neuropathy target esterase (NTE) of hen brain in vitro and in vivo. PSM was a potent inhibitor of AChE, with an I50 of 2.9μM and second-order rate constant (ka) of 1.2×104 M-1 min-1 at 37°C. PSM-inhibited AChE aged rapidly (t1/2=1.9h). Pyridinium oximes pralidoxime, trimedoxime, obidoxime and HI-6 were effective reactivators of PSM-inhibited AChE, providing up to 75% reactivation. PSM was one of the weakest inhibitors of NTE among organophosphorus compounds, with an I50 of 19 mM and ka of 1.8 M-1 min-1 at 37°C. Inhibited NTE did not reactivate spontaneously and KF-induced reactivation was not obtained even at the earliest tested moments, so it was not clear whether aging of PSM-inhibited NTE occurred very quickly or the KF molecule could not affect the stability of phosphoryl-NTE bond. From the ratio of kas for NTE and AChE (0.00015) it was predicted that delayed neuropathic effects of PSM in vivo would appear only at doses far above the acute LD50. The LD50 value of PSM p.o. for hens was 9 mg/kg. Hens were treated with a single oral dose of PSM, combined with standard antidotal treatment which included atropine, physostigmine, pralidoxime and anticonvulsant midazolam. Doses of 90 and 250 mg/kg caused up to 27% and 45% NTE inhibition 48h after poisoning, respectively. Clinical signs of neuropathy were not seen up to 25 days after treatment, which could be expected, since the proposed level (>70%) of NTE inhibition necessary for the occurrence of delayed neuropathy was not achieved. The results suggest that PSM, at doses tested, has no ability to cause delayed neuropathy in hens without showing signs of severe cholinergic intoxication.",
publisher = "Springer-Verlag",
journal = "Archives of Toxicology",
title = "Interaction of phosphamidon with neuropathy target esterase and acetylcholinesterase of hen brain",
volume = "69",
number = "6",
pages = "425-428",
doi = "10.1007/s002040050195"
}
Jokanović, M., Maksimović, M.,& Stepanović-Petrović, R.. (1995). Interaction of phosphamidon with neuropathy target esterase and acetylcholinesterase of hen brain. in Archives of Toxicology
Springer-Verlag., 69(6), 425-428.
https://doi.org/10.1007/s002040050195
Jokanović M, Maksimović M, Stepanović-Petrović R. Interaction of phosphamidon with neuropathy target esterase and acetylcholinesterase of hen brain. in Archives of Toxicology. 1995;69(6):425-428.
doi:10.1007/s002040050195 .
Jokanović, Milan, Maksimović, Matej, Stepanović-Petrović, Radica, "Interaction of phosphamidon with neuropathy target esterase and acetylcholinesterase of hen brain" in Archives of Toxicology, 69, no. 6 (1995):425-428,
https://doi.org/10.1007/s002040050195 . .

DSpace software copyright © 2002-2015  DuraSpace
About FarFaR - Pharmacy Repository | Send Feedback

OpenAIRERCUB
 

 

All of DSpaceCommunitiesAuthorsTitlesSubjectsThis institutionAuthorsTitlesSubjects

Statistics

View Usage Statistics

DSpace software copyright © 2002-2015  DuraSpace
About FarFaR - Pharmacy Repository | Send Feedback

OpenAIRERCUB