Affinity of myasthenia drugs to acetylcholinesterase and acetylcholine receptor

Seifert, S.; Eldefrawi, Mohyee E.

doi:10.1016/0006-2944(74)90029-5

Cited by 14 publications

(4 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other carbamates with tertiary amines such as pyridostigmine and neostigmine, and the noncarbamate edrophonium also have the capability of AChR activation but at higher concentration ranges than (À)physostigmine (Akaike et al, 1984;. However, earlier evidence indicated that these compounds blocked ACh binding to AChR (Seifert and Eldefrawi, 1974). Interestingly, benzoquinonium enhanced the binding of the high-anity NCI histrionicotoxin to the AChR ion channel in the absence of agonists, indicating that benzoquinonium may activate and subsequently desensitize the receptor (Pereira et al, 1993).…”

Section: Localization Of the Noncompetitive Agonist Binding Sitementioning

confidence: 99%

Localization of agonist and competitive antagonist binding sites on nicotinic acetylcholine receptors

Arias

2000

Neurochemistry International

187

157

View full text Add to dashboard Cite

Section: Localization Of the Noncompetitive Agonist Binding Sitementioning

confidence: 99%

Localization of agonist and competitive antagonist binding sites on nicotinic acetylcholine receptors

Arias

2000

Neurochemistry International

187

157

View full text Add to dashboard Cite

“…However, early studies suggested that the anti-ChE carbamates have additional direct activating or inhibiting effects on the nicotinic AChR (17). Based on the mechanism of drug binding to AChR site(s), certain properties of ligand specificity in binding to the allosteric channel sites have been discovered.…”

Section: Introductionmentioning

confidence: 99%

Biochemical interactions of carbamates and ecothiophate with the activated conformation of nicotinic acetylcholine receptor

Mansour

Valdés

Shamoo

et al. 1987

J. Biochem. Toxicol.

View full text Add to dashboard Cite

Purified Torpedo nobiliana electric organ acetylcholine receptor (AChR) was reconstituted into membranes containing natural phospholipids supplemented with cholesterol (25% w/w). The reconstituted system facilitates the study of the effects of drugs on the regulation of the AChR channel complex under both resting and carbachol (carb)-stimulated conditions. Neostigmine (Neo) was the only carbamate to induce activation of [3-H]-phencyclidine ([3-H]-PCP) binding to the channel sites, acting as a weak agonist. The activation of [3-H]-PCP binding is dependent upon the nature of the reconstituted systems, with carb/Neo activation ratios of 8, 3, and 1 for the intact purified AChR vesicles fraction (PVF), the PVF reconstituted in phospholipid/cholesterol (CRPVF), and the PVF reconstituted in phospholipid (RPVF), respectively. The carbamates Neo, physostigmine (Physo), and pyridostigmine (Pyrido) inhibited carb-activated [3-H]-PCP binding with Ki values of 10, 20, and 1,600 microM, respectively. The inhibition was mixed competitive-noncompetitive in nature. The characteristic response of CRPVF to carb-stimulated [22-Na] influx was inhibited by the three carbamates, with IC-50 values of 6, 50, and 1,000 microM for Neo, Physo, and Pyrido, respectively. The quaternary ammonium organophosphate ecothiophate (Eco) inhibited carb-stimulated [22-Na] influx with potency similar to that of Neo. Preincubation of AChR preparation with the carbamates and ecothiophate caused a reduction in the binding of [125-I]-alpha-bungarotoxin ([125-I]-alpha-BGT) with the following decreasing order of potency: Neo less than Physo less than Eco less than Pyrido. Calcium has a direct modulatory role on the time-course inhibition of [125-I]-alpha-BGT binding by these drugs. While we observed a high potency of Neo and Physo in inhibiting [125-I]-alpha-BGT binding, it was undetectable for the carbamate insecticide 2-methyl-2-(methylthio)propionaldehyde-O-(methylcarbamoyl)oxime (aldicarb). These data suggest that the potent anticholinesterase carbamate agents interact differently with the AChR and its ionic channel. Their interactions with the nicotinic AChR channel system can be described as (a) weakly agonist, (b) directly acting on the open conformation of the channel, and (c) blocking the AChR-binding sites.

show abstract

“…Today there are a lot of possibilities for example to use sonic weapons from the space satellites, like is category of Russian ERA-GLONASS satellites, (they can blockade completely the whole electronic system of the terrestrial cars), etc. [5,6] The Traditional Medicine has not enough information and means to heal these new types of health disorders caused by Sonic Weapons. We also propose to update the International Diseases' Register of the WHO with new Diagnosis of Carcinogenesis caused by Sonic Weapons.…”

Section: Discussionmentioning

confidence: 99%

The Frey Effect of Microwave Sonic Weapons

Salais

2018

DDIPIJ

View full text Add to dashboard Cite

State Department evacuates a number of Americans from the U.S. consulate in Guangzhou, China after they experienced unexplained health issues. A group of U.S. diplomats stationed in China have been brought back to the states after being inflicted by a mystery illness that reportedly resembles the brain injuries previously suffered by staff in Cuba. Heather Nauert, a State Department spokeswoman, said in a statement that the individuals from the U.S. office in Guangzhou were returned home for further evaluation. It was unclear if there was any connection to last year's situation in Cuba where 24 US government employees experienced a range of ailments after hearing an unusual sound.

show abstract

Affinity of myasthenia drugs to acetylcholinesterase and acetylcholine receptor

Cited by 14 publications

References 16 publications

Localization of agonist and competitive antagonist binding sites on nicotinic acetylcholine receptors

Localization of agonist and competitive antagonist binding sites on nicotinic acetylcholine receptors

Biochemical interactions of carbamates and ecothiophate with the activated conformation of nicotinic acetylcholine receptor

The Frey Effect of Microwave Sonic Weapons

Contact Info

Product

Resources

About