Changes of cholinesterases in the blood and some tissues following administration of tacrin and its two derivatives to rats

Bajgar, Jiří; Fusek, J.; Skopec, F

doi:10.1016/0197-0186(94)90007-8

Cited by 10 publications

(9 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Kassa et al (22) described normal AChE activity in the whole brain homogenate (54 μkat/kg) slightly lower than our activity in the cerebellum (61.5 μkat/kg). The AChE inhibition in the pontomedullar area following tacrine administration was very similar to our former results (2). It was also proved that the central effect of tacrine is higher than that of pyridostigmine -pyridostigmine practically does not cause AChE inhibition in the brain, i.e.…”

Section: Discussionsupporting

confidence: 75%

“…The doses (except VX) represent the doses approximately to be used for human prophylaxis (2,3,8,15,23). They were as follows:…”

Section: Doses Of Drugs Usedmentioning

confidence: 99%

“…The doses and timing of drug administration were used on the basis of our previous results with tacrine (2), reactivators including HI-6 (3, 15), pyridostigmine, benactyzine and trihexyphenidyle (3,23,24), and EqBuChE (8,12), respectively. The doses (except VX) represent the doses approximately to be used for human prophylaxis (2,3,8,15,23).…”

Section: Doses Of Drugs Usedmentioning

confidence: 99%

See 2 more Smart Citations

Protective Effect of Reversible Cholinesterase Inhibitors (Tacrine, Pyridostigmine) and EqBuChE against VX Poisoning and Brain Acetylcholinesterase Inhibition in Rats

Bajgar

2008

Acta Med. (Hradec Kralove, Czech Repub.)

View full text Add to dashboard Cite

The protective effect of the reversible cholinesterase inhibitors tacrine and pyridostigmine alone or in combination with different drugs against acetylcholinesterase inhibition in the pontomedullar area and cerebellum of rats caused by VX agent (O-ethyl S-2-diisopropylaminoethyl methyl phosphonothiolate) in vivo (2xLD50) was studied along with survival of animals pretreated with different combinations of the drugs used. The best prophylactic effect was observed in a combination of pyridostigmine with benactyzine, trihexyphenidyle and HI-6. Tacrine alone or in other combinations has had no better prophylactic effect in comparison with these combinations containing pyridostigmine. Equine butyrylcholinesterase, also protected against VX poisoning very effectively.

show abstract

Section: Discussionsupporting

confidence: 75%

“…The doses (except VX) represent the doses approximately to be used for human prophylaxis (2,3,8,15,23). They were as follows:…”

Section: Doses Of Drugs Usedmentioning

confidence: 99%

Section: Doses Of Drugs Usedmentioning

confidence: 99%

See 1 more Smart Citation

Protective Effect of Reversible Cholinesterase Inhibitors (Tacrine, Pyridostigmine) and EqBuChE against VX Poisoning and Brain Acetylcholinesterase Inhibition in Rats

Bajgar

2008

Acta Med. (Hradec Kralove, Czech Repub.)

View full text Add to dashboard Cite

show abstract

“…obidoxime and pralidoxime are effective against cyclosarin-and sarin-inhibited AChE at concentrations reaching to 10 -3 -10 -2 M. Lower concentrations of reactivators are also able to reactivate inhibited AChE but the percentage of reactivation is not so high -it reaches to 10-20% of reactivation at lower concentrations (10 -4 -10 -5 M). The non-uniform AChE inhibition or reactivation in different brain areas was observed not only for OP and oximes but also for other cholinesterase inhibitors (tacrine, galanthamine, 7-methoxytacrine) or its influencing by other factors such as a pretreatment with L-carnitine [77,78].…”

Section: H-oximesmentioning

confidence: 92%

Cholinesterase Reactivators: The Fate and Effects in the Organism Poisoned with Organophosphates/Nerve Agents

Bajgar

Kuča

Jun³

et al. 2007

CDM

Self Cite

View full text Add to dashboard Cite

Understanding the mechanism of action of organophosphates (OP)/nerve agents -irreversible acetylcholinesterase (AChE, EC 3.1.1.7) inhibition at the cholinergic synapses followed by metabolic dysbalance of the organism -two therapeutic principles for antidotal treatment are derived. The main drugs are anticholinergics that antagonize the effects of accumulated acetylcholine at the cholinergic synapses and cholinesterase reactivators (oximes) reactivating inhibited AChE. Anticonvulsants such as diazepam are also used to treat convulsions. Though there are experimental data on a good therapeutic effects of reactivators, some attempts to underestimate the role of reactivators as effective antidotes against OP poisoning have been made. Some arguments on the necessity of their administration following OP poisoning are discussed. Their distribution patterns and some metabolic and pharmacological effects are described with the aim to resolve the question on their effective use, possible repeated administration in the treatment of OP poisonig, their peripheral and central effects including questions on their penetration through the blood brain barrier as well as a possibility to achieve their effective concentration for AChE reactivation in the brain. Reactivation of cholinesterases in the peripheral and central nervous system is described and it is underlined its importance for the survival or death of the organism poisoned with OP. Metabolization and some other effects of oximes (not connected with AChE reactivation) are discussed (e.g. forming of the phosphonylated oxime, parasympatholytic action, hepatotoxicity, behavioral changes etc.). An universality of oximes able to reactivate AChE inhibited by all OP is questioned and therefore, needs of development of new oximes is underlined.

show abstract

“…It was characterized in vitro and in vivo 4 . It has lower hepatotoxicity in comparison with tacrine, but its peripheral parasympathomimetic effect is a potential clinical complication 5 .…”

Section: Intestinal Single-pass In Situ Perfusion Technique In Rat: Tmentioning

confidence: 99%

Intestinal Single-Pass in Situ Perfusion Technique in Rat: The Influence of L-Carnitine on Absorption of 7-Methoxytacrine

Kunes¹,

Svoboda²,

Kvĕtina³

et al. 2005

BIOMED PAP

View full text Add to dashboard Cite

Key words: Methoxytacrine/Carnitine/Single-pass perfusion/Rat small intestine/Intestinal absorption 7-Methoxytacrine (7-MEOTA) is an acetylcholine-esterase inhibitor that is potentially useful in the therapy of some neurodegenerative disorders. L-carnitine (CRT) is a naturally occuring compound that is known to increase penetration of some compounds through biological barriers. Aim of this study was how CRT influenced transintestinal absorption transport 7-MEOTA in rat using single-pass intestinal in situ perfusion method. The rate of absorption of 7-MEOTA during luminal perfusion with single 7-MEOTA was compared with rate of absorption during simultaneous perfusion with 7-MEOTA and CRT and with absorption rate after the premedication with CRT for period of three days before beginning of perfusion. The methodical system was the perfusion of mesenterial bed (from arteria mesenterica superior to vena portae) and intestinal luminal perfusion (from duodenum to ileum). The lower transintestinal absorption in the course of simultaneously administration of CRT than just in case of perfusion with single 7-MEOTA has been found. On the contrary a significantly higher absorption of 7-MEOTA has been noted in group of rats premedicated with CRT for three consecutive days. The interpretation suggested that molecules of CRT incorporated into the metabolism of intestinal cells facilitated transport of 7-MEOTA (as a representative substance which is at least partly transferred by carrier mechanism). In case of simultaneous luminal perfusion with CRT and 7-MEOTA competitive over-saturation of carrier systems is probably.

show abstract

Changes of cholinesterases in the blood and some tissues following administration of tacrin and its two derivatives to rats

Cited by 10 publications

References 14 publications

Protective Effect of Reversible Cholinesterase Inhibitors (Tacrine, Pyridostigmine) and EqBuChE against VX Poisoning and Brain Acetylcholinesterase Inhibition in Rats

Protective Effect of Reversible Cholinesterase Inhibitors (Tacrine, Pyridostigmine) and EqBuChE against VX Poisoning and Brain Acetylcholinesterase Inhibition in Rats

Cholinesterase Reactivators: The Fate and Effects in the Organism Poisoned with Organophosphates/Nerve Agents

Intestinal Single-Pass in Situ Perfusion Technique in Rat: The Influence of L-Carnitine on Absorption of 7-Methoxytacrine

Contact Info

Product

Resources

About