Linked Life Data

8067894

Source:http://linkedlifedata.com/resource/pubmed/id/8067894

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1994-9-19
pubmed:abstractText
The oximes HI-6, HLö-7, HGG-12, HGG-42 and obidoxime were used in a previously developed rat model to evaluate the therapeutic effects of oximes other than acetylcholinesterase (AChE) reactivation (so-called "non-reactivating effects"). To test this anaesthetized, atropinized and artificially ventilated rats (n = 8 or 16) were poisoned with a three times LD50 dose of the potent AChE-inhibitor crotylsarin (CRS, i.v.). CRS-inhibited rat AChE dealkylates instantaneously, thereby excluding AChE reactivation by the oximes. Five minutes after poisoning the rats were treated (i.v.) with an oxime or saline and 10 min later artificial ventilation was terminated. Survival times were determined. Saline-treated animals died within 15 min. In comparison, treatment with HI-6, HLö-7, HGG-12, HGG-42 or obidoxime resulted in a significant prolongation of survival time. In the groups treated with HLö-7, HI-6 or HGG-12, 12-37% of the animals survived more than 24 h. It was investigated whether differences in therapeutic effectiveness are caused by differences in pharmacokinetics of the oximes. The plasma half-lives of HI-6, HLö-7, HGG-12, HGG-42 and obidoxime amounted to 67, 63, 27, 55 and 179 min, respectively. At doses of 75 or 150 mumol/kg, all oximes could be detected in brain and medulla oblongata in similar amounts (6-10 nmol/g tissue). In vitro, all oximes were effective in restoring failure of neuromuscular transmission (NMT) caused by CRS, albeit with varying potency. All oximes bound with affinities in the micromolar range to rat brain muscarinic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Cholinesterase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Cholinesterase Reactivators, http://linkedlifedata.com/resource/pubmed/chemical/HGG 12, http://linkedlifedata.com/resource/pubmed/chemical/HGG 42, http://linkedlifedata.com/resource/pubmed/chemical/HI 6, http://linkedlifedata.com/resource/pubmed/chemical/HLo 7, http://linkedlifedata.com/resource/pubmed/chemical/Obidoxime Chloride, http://linkedlifedata.com/resource/pubmed/chemical/Oximes, http://linkedlifedata.com/resource/pubmed/chemical/Pyridines, http://linkedlifedata.com/resource/pubmed/chemical/Pyridinium Compounds, http://linkedlifedata.com/resource/pubmed/chemical/Quinuclidinyl Benzilate, http://linkedlifedata.com/resource/pubmed/chemical/Sarin, http://linkedlifedata.com/resource/pubmed/chemical/crotylsarin
pubmed:status
MEDLINE
pubmed:issn
0340-5761
pubmed:author
pubmed:issnType
Print
pubmed:volume
68
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
224-30
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Comparison of the therapeutic effects and pharmacokinetics of HI-6, HLö-7, HGG-12, HGG-42 and obidoxime following non-reactivatable acetylcholinesterase inhibition in rats.
pubmed:affiliation
TNO Medical Biological Laboratory, Rijswijk, The Netherlands.
pubmed:publicationType
Journal Article, Comparative Study, In Vitro, Research Support, Non-U.S. Gov't