Anticholinesterases interaction

Harris, L.W., Lennox, W.J. and B.G. Talbot. 1984. Toxicity of anticholinesterase Interactions of pyrdiostigmine and physostigmine with soman. Drug Chem. Toxicol. 7 507—526. (cited in Somani et al., 1992)... 

Harris L, Lennox W, Talbot BG et al. (1984). Toxicity of anticholinesterases interaction of pyridostigmine and physostigmine with soman. Drug Chem Toxicol, 7, 507-526. 

Sussman, J.L., Harel, M., and Silman, I. (1993). Three-dimensional structure of acetylcholinesterase and of its complexes with anticholinesterase drugs. Chemico-Biological Interactions 87, 187-197. 

Albuquerque EX, Akaike A, Shaw KP, Rickett DL. The interaction of anticholinesterase agents with the acetylcholine receptor-channel complex. Fundam. Appl. Toxicol. 4 S27-S33, 1984. 

Savelev S, Okello E, Perry NSL, Synergistic and antagonistic interactions of anticholinesterase terpenoids in Salvia lavandulaefolia essential oil, Pharmacol Biochem Behavior 75.SSI—66S, 2003. 

Since mivacurium is metabolized by plasma cholinesterase, the interaction with the anticholinesterase reversal drugs is less... 

Thus, exposure to any of these enzyme inducers concurrent with or after exposure to diazinon may result in accelerated bioactivation to the more potent anticholinesterase diazoxon. The extent of toxicity mediated by this phenomenon is dependent on how fast diazoxon is hydrolyzed to less toxic metabolites, a process that is also accelerated by the enzyme induction. Similarly, concurrent exposure to diazinon and MFO enzyme-inhibiting substances (e.g., carbon monoxide ethylisocyanide SKF 525A, halogenated alkanes, such as CC14 alkenes, such as vinyl chloride and allelic and acetylenic derivatives) may increase the toxicity of diazinon by decreasing the rate of the hydrolytic dealkylation and hydrolysis of both parent diazinon and activated diazinon (diazoxon) (Williams and Burson 1985). The balance between activation and detoxification determines the biological significance of these chemical interactions with diazinon. 

AH of the nerve agents under consideration are anticholinesterase compounds and induce accumulation of the neurotransmitter acetylcholine (ACh) at neural synapses and neuromuscular junctions by phosphorylating acetylcholinesterase (AChE). Depending on the route of exposure and amount absorbed, the PNS and/or CNS can be affected and muscarinic and/or nicotinic receptors may be stimulated. Interaction with other esterases may also occur, and direct effects to the nervous system have been observed. 

Kaufer, D., Friedman, A., Seidman, S., Soreq, H. (1999). Anticholinesterase induce multigenic transcriptional feedback response suppressing cholinergic neurotransmisison. Chem. Biol. Interact. 199-20 349-60. 

Action on receptors provides numerous examples. Beneficial interactions are sought in overdose, as with the use of naloxone for morphine overdose (opioid receptor), of atropine for anticholinesterase, i.e. insecticide poisoning (acetylcholine receptor), of isoproterelol (isoprenaline) for overdose with a P-adrenoceptor blocker (p-adrenoceptor), of phentolamine for the monoamine oxidase inhibitor-sympathomimetic interaction (a-adrenoceptor). 

Clinically important, potentially hazardous interactions with acetazolamide, aminoglycosides, anticholinesterases, bambuterol, calcium channel blockers, chloroquine, chlorpromazine, clindamycin, d-pencillamine, ecothiophate iodine, enflurane, furosemide, halothane, hexomethonium, isoflurane, ketamine, lidocaine, lincomycin, lithium salts, magnesium salts, mannitol, MAO inhibitors, organophosphates, pancuronium, phenytoin, polymyxins, procainamide, quinidine, sevoflurane, spectinomycin, tetracyclines... 

The design of anticholinesterases depends on the shape of the enzyme active site, the binding interactions involved with acetylcholine, and the mechanism of hydrolysis. 

These are compounds which are grouped according to the enzyme or receptor with which they interact. For example, anticholinesterases (Chapter 11) are a group of drugs which act through inhibition of the enzyme acetylcholinesterase. 

Meeter I agree that there must be a peripheral component. I mentioned that atropine sulphate is unable to prevent the anticholinesterase hypothermia completely in fact it reduces the lowering of the body temperature only by about 50%. In a recent experiment we administered soman intraventricular-ly in order to obtain a purely central hypothermia. It appeared that this hypothermia could be prevented completely by intraventricular as well as by intraperitoneal atropine sulphate. How methyl atropine interacts with the peripheral component is still unknown I intend to study that in the future. 

Anticholinesterase drugs work by inhibiting the enzyme that normally destroys acetylcholine after it has stimulated its receptors at the neuromuscular junction. This leads to increased amounts of acetylcholine available to interact with remaining receptors and so improves the ability of muscles to contract. An example of an anticholinesterase drug is... 

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