Armin is a reversible organophosphorus cholinesterase inhibitor. It also affects the presynaptic membrane and inhibits membrane postsynaptic cholinergic receptors. The compound had former use as a miotic
We compared the effects of the novel acetylcholinesterase (AChE) inhibitor C-547 on action potential configuration and sinus rhythm in the isolated right atrium preparation of rat with those of armin and neostigmine. Both armin (10(-7), 10(-6), and 10(-5) M) and neostigmine (10(-7), 10(-6), and 5 x 10(-6) M) produced a marked decrease in action potential duration and slowing of sinus rate. These effects were abolished by atropine and are attributable to the accumulation of acetylcholine in the myocardium. The novel selective AChE inhibitor C-547 (10(-9) to 10(-7) M), an alkylammonium derivative of 6-methyluracil, had no such effects. The inhibition constant of C-547 on cardiac AChE is 40-fold higher than that on extensor digitorum longus muscle AChE. These results suggest that C-547 might be employed to treat diseases such as myasthenia gravis or Alzheimer disease, without having unwanted effects on the heart.
Title: [Protection of mice by carbamates cholinesterase inhibitors against poisoning by armin and its dependence on certain physico-chemical indicators] Prozorovskii VB, Pavlova LV, Suslova IM, Sazonova AV, Kokushkina AV Ref: Vopr Med Khim, 45:525, 1999 : PubMed
A series of aminostigmin derivatives with various substituents at nitrogen in the second position of the pyridine ring, has been tested. The efficacy of preventing the death of mice poisoned by armine in five of the seven substances correlates with the constant of the rate of carbamylation of acetylcholinesterase in the in vitro experiments and with the hydrophobic nature. It is suggested that the phenomenon of protection of animals against the toxic effect of organophosphorous compounds involves the "leaving portion" of the molecule of carbamates.
Catalytic properties of human blood erythrocyte acetylcholinesterase and horse blood serum butyrylcholinesterase immobilized and nonimmobilized in the gelatin membrane have been comparatively studied. Cholinesterase immobilization induces an increase in the Michaelis constant value and a decrease in the maximum rate value in reactions of enzymic hydrolysis of thiocholine ethers, but exerts no effect on these kinetic parameters in case of enzymic hydrolysis of indophenylacetate. The effect of reversible inhibitors: galanthamine, N-methyl-4-piperidinyl benzylate and 1,2,3,4-tetrahydro-9-aminoacridine (tacrine), as well as of irreversible inhibitors: O-ethyl-O-(4-nitrophenyl)ethyl phosphonate (armin), diisopropyl fluorophosphate (DFP), O,O-diethyl-O-(4-nitrophenyl) phosphate (paraoxon) and O,O-dimethyl-O-(2,2-dichlorovinyl) phosphate (DDVP) on immobilized cholinesterases is weaker as compared with the effect on nonimmobilized enzymes. The results obtained are discussed for the effect of immobilization on the catalytically active enzyme surface.
We compared the effects of the novel acetylcholinesterase (AChE) inhibitor C-547 on action potential configuration and sinus rhythm in the isolated right atrium preparation of rat with those of armin and neostigmine. Both armin (10(-7), 10(-6), and 10(-5) M) and neostigmine (10(-7), 10(-6), and 5 x 10(-6) M) produced a marked decrease in action potential duration and slowing of sinus rate. These effects were abolished by atropine and are attributable to the accumulation of acetylcholine in the myocardium. The novel selective AChE inhibitor C-547 (10(-9) to 10(-7) M), an alkylammonium derivative of 6-methyluracil, had no such effects. The inhibition constant of C-547 on cardiac AChE is 40-fold higher than that on extensor digitorum longus muscle AChE. These results suggest that C-547 might be employed to treat diseases such as myasthenia gravis or Alzheimer disease, without having unwanted effects on the heart.
Title: [Protection of mice by carbamates cholinesterase inhibitors against poisoning by armin and its dependence on certain physico-chemical indicators] Prozorovskii VB, Pavlova LV, Suslova IM, Sazonova AV, Kokushkina AV Ref: Vopr Med Khim, 45:525, 1999 : PubMed
A series of aminostigmin derivatives with various substituents at nitrogen in the second position of the pyridine ring, has been tested. The efficacy of preventing the death of mice poisoned by armine in five of the seven substances correlates with the constant of the rate of carbamylation of acetylcholinesterase in the in vitro experiments and with the hydrophobic nature. It is suggested that the phenomenon of protection of animals against the toxic effect of organophosphorous compounds involves the "leaving portion" of the molecule of carbamates.
Title: [The effect of armin on neuromuscular transmission in the frog against a background of hexadecamethonium action]. [Russian] Grigor'ev VM Ref: Fiziologicheskii Zhurnal, 81:27, 1995 : PubMed
Hexadecamethonium as well as its alkylating derivatives significantly decrease the effect of organophosphorous acetylcholinesterase inhibitor armine on the amplitude and duration of the EPPs. It seems possible that these substances prevent inhibition of acetylcholinesterase. This property of the substances seems to be due to a polymethelene chain with two nitrogens as the basic part of the molecule structure.
Catalytic properties of human blood erythrocyte acetylcholinesterase and horse blood serum butyrylcholinesterase immobilized and nonimmobilized in the gelatin membrane have been comparatively studied. Cholinesterase immobilization induces an increase in the Michaelis constant value and a decrease in the maximum rate value in reactions of enzymic hydrolysis of thiocholine ethers, but exerts no effect on these kinetic parameters in case of enzymic hydrolysis of indophenylacetate. The effect of reversible inhibitors: galanthamine, N-methyl-4-piperidinyl benzylate and 1,2,3,4-tetrahydro-9-aminoacridine (tacrine), as well as of irreversible inhibitors: O-ethyl-O-(4-nitrophenyl)ethyl phosphonate (armin), diisopropyl fluorophosphate (DFP), O,O-diethyl-O-(4-nitrophenyl) phosphate (paraoxon) and O,O-dimethyl-O-(2,2-dichlorovinyl) phosphate (DDVP) on immobilized cholinesterases is weaker as compared with the effect on nonimmobilized enzymes. The results obtained are discussed for the effect of immobilization on the catalytically active enzyme surface.
Title: [Effect of armin and dipyroxime on the nicotinamide coenzyme and adenine nucleotide content of the rat myocardium and liver]. [Russian] Tikhonenko VM Ref: Farmakologiia i Toksikologiia, 45:26, 1982 : PubMed
It has been shown in rat experiments that armin in
doses that inhibit blood cholinesterase by 50 and more per
cent lowers the content of nicotinamide coenzymes in the myocardium
and liver of the animals primarily at the expense of
the diminution of the oxidized forms In the rat liver
armin decreases the content of adenyl nucleotides mainly at the
expense of ATP Dipyroxime prevents changes induced by armin which
is accompanied by partial reactivation of cholinesterase It is suggested
that in the mechanism of antidote action of dipyroxime of
importance is its normalizing effect on redox and energy processes
in the body
