[Mechanism of the "acetylene effect" during interaction of organophosphorus compounds with cholinesterases].

Here we present data on the anticholinesterase activity of 58 synthesized ethers of phosphorus thioacids with an acetylene bond in the thioether group. Anticholinesterase activity of the compounds, with acetylene group in beta and especially alpha position, in the thioether radical is many times that of their saturated analogs. Reaction between the enzymes and acetylene organophosphorous inhibitors, as well as their saturated analogs, results in phosphorylated enzyme.

[Biochemical characteristics of aminostigmine--a new anticholinesterase agent].

The properties of aminostigmine in comparison with those of other carbamate inhibitors of cholinesterases have been studied in vitro using potentiometric titration and Ellman methods. The bimolecular constants of the inhibition rate of acetyl-, butyryl- and propionylcholinesterase were found to be equal to (8.0-14.

[A comparative study of carboxylesterase in the white mouse and in the caterpillar of the cotton bollworm Heliothes armigera].

Studies have been made on enzymic hydrolysis of p-nitrophenylacetate (p-NPhAc), n-nitrophenylbutyrate (p-NPhBu) and indophenylacetate (IPhAc) by carboxylesterase (CE) from mouse blood plasma and liver as well as from caterpillar of the cotton worm haemolymph, intestine and fat body. Different KM and V max values were obtained for CE from these sources. The highest specific activity of CE from mouse liver and caterpillar intestine and fat body was observed with p-NPhBu.

[The mechanism of anticholinesterase action of acetylene organophosphorus inhibitors].

Introduction of the triple bond in the leaving group of the organophosphorus inhibitor molecule gives a sharp raise of the inhibitor activity but does not change principal characteristics of the cholinesterase inhibition mechanism. The reactivation experiments suggest that inactivation of cholinesterases by these compounds occurs due to phosphorylating of the serine hydroxyl by the corresponding phosphoric acid. A close similarity was shown between acetylenic and saturated organophosphorus inhibitors in altering ka upon change of pH and tetraalkylammonium ions action.

[The effect of pH and reversible inhibitors on decarbamylation of acetylcholinesterase].

Decarbamylation rate of membrane-bound methyl- and dimethyl-carbamylated acetylcholinesterase of human erythrocytes and bovine brain is reliably 1.1-1.6 times lower than that of the soluble enzyme.

[The lymphocyte acetylcholinesterase activity in rats poisoned by pesticides].

The experiments carried out present the evidence of acetylcholinesterase activity of Wistar rat lymphocytes. It was shown that splenocytes and thymocytes had significantly different levels of the enzyme activity. Peroral administration of phosphor-organic pesticide antio (phormothion) 1/100 and 1/20 LD50 induced the dose-dependent inhibition of splenocyte acetylcholine-esterase activity after 2 months of treatment.

[Acetylenic amines as inhibitors of microsomal monooxygenases].

A new class of compounds: acetylenic amines, possessing structural similarity with the known inhibitor SKF-525A, and their saturated analogues, has been studied for its effect on the microsomal cytochrome P-450-dependent monooxygenases (MM). Significant differences in sensitivity of different substrate oxidation reactions in experiments with the mouse liver MM were observed. It was shown that the acetylenic amines investigated 13-30 times exceeded their saturated analogues as to the ability to inhibit aminopyrine and benzo[a]pyrene oxidation, and differed but slightly from their analogues with respect to p-nitroanisole and paraoxon oxidation.

[A comparative study of the effect of vinyl phosphoric acid esters on cholinesterase and carboxylesterase activities in mammals and arthropods].

Studies have been made of the effect of organophosphorus inhibitors on cholinesterase and carboxylesterase from various mammals (human erythrocytes, mouse brain, blood serum of mouse and rat, blood serum of horse) and arthropods (Calliphora vicina, Schizaphis graminum, Myzus persicae, Sitophilus oryzae, Pseudococcus maritimus, Tetranychus urticae). Organophosphorus inhibitors were presented by esters of vynylphosphoric acid containing normal and branched alkyls in the phosphoryl part of the molecule. The increase of the radical up to a propyl one increased the effect of organophosphorus inhibitors with respect to cholinesterase from the majority of the arthropods investigated.

[Interaction of membrane-bound and solubilized erythrocyte acetylcholinesterase with carbamates].

Physostigmine and neostigmine methylsulphate are shown to be the most strong inhibitors of acetylcholine esterase of human erythrocytes. The action of baigon is less pronounced and pyrimor is characterized as the weakest inhibitor. No differences are found between the membrane-bound and solubilized acetylcholine esterase relative to their ability to be inhibited by these carbamates.

[Interaction of membrane-bound and solubilized acetylcholinesterase from human and bovine erythrocytes with organophosphorus inhibitors].

Differences are found between the membrane-bound and soluble acetylcholinesterases of human and bovine erythrocytes when the enzyme interacts with organophosphoric inhibitors in the presence of acetylc choline and galantamine, a reverse inhibitor of acetylcholinesterase. In most cases prevention of inhibition of the soluble enzyme activity necessitates a higher (2-3 times higher) concentration of the protecting agent than protection of the membrane-bound enzyme. Concentrations of acetylcholine and galantamine providing a 50% protection of the enzyme did not practically depend on the strength of the anticholinesterase action of organophosphoric inhibitors.

[Effect of organophosphorus inhibitors, lupinine and epilupinine derivatives, on mammalian and arthropod cholinesterases].

Studies have been made on the effect of organophosphorus inhibitors on cholinesterases (CHe) from mammals (human and rabbit erythrocytes, mice brain) and arthropods (fly, spring grain aphid, rice weevil and spider tick). Organophosphorus inhibitors were presented by dialkylthiophosphates which contained normal or branching alkyls in the phosphoryl part of their molecule and lupinine or epilupinine residue in the other part of the latter. Increasing the length of alkyl in lupinine derivatives increased their inhibitory effect with respect to mammalian CHe, but decreased it in relation to all the investigated arthropod CHe.

[Intracellular distribution of phosphoorganic cholinesterase inhibitors in rat brain].

Content of organophosphorous inhibitors (with the structure RO/CH3/P/O/SC2H4SC2H5) of cholinesterase as well as their hydrophobic properties (distribution coefficient in hexan/water system) were studied in subcellular fractions of rat brain. Relative content of organophosphorous inhibitors was distinctly decreased in supermicrosomal fraction with increase of hydrophobic properties of the fraction. Nuclear and mitochondrial fractions contained the more hydrophobic substances in relatively higher amount.

[Proton acceptor properties of the blood plasma of a series of vertebrates].

Comparative studies have been made on the kinetics of thermal denaturation of the blood plasma of various vertebrates (lampreys, teleosts, frogs, tortoises, pigeons, mice, rats, rabbits, cats, dogs, man) by measuring ionization equilibrium of protein solution at elevated temperature. It was demonstrated that during the initial stage of heat denaturation at 58 degrees the blood plasma of all the animals studied binds protons practically linearly. Among the animals studied, the highest protonoacceptor capacity exhibited the plasma of warm-blooded animals; it was lower in tortoises frogs and teleost fishes, being the lowest one in lampreys.

[Effect of environment on allosteric properties of acetylcholinesterase].

In the presence of organophosphorus inhibitors (OPI) AChE inhibition is initiated at a lower concentration of ACh; the plot reaction rate versus substrate concentration shows two maxima with a distinct minimum between them. It was shown that extremely mild conditions (short-term heating up to 50 degrees C; acidic or alkaline pH shift by 0.5 units; high concentrations of bivalent cations; erythrocyte storage) which do not affect substrate inhibition, remove this effect.

[Effect of diazepam on the properties of an erythrocyte-plasma protein complex and the development of shock during the transfusion of heterogenic blood].

Preliminary administration of 2 mg/kg of diazepam eliminated the pyrogenic reaction and increased survival of rabbits following intravenous injection of cat blood to them. A study of physico-chemical properties of the blood by measurement of the ionization balance in thermal denaturing demonstrated that injection of heterogenous blood to rabbits and suspension of rabbit erythrocytes in cat plasma in vitro led to a sharp reduction of the rate of proton binding with plasma proteins in the presence of foreign erythrocytes. Preliminary administration of diazepam to rabbits, and diazepam addition to the cat plasma in vitro prevented such changes and promoted retention of normal blood properties.

[Binding of phosphoorganic cholinesterase inhibitors in rat brain tissue].

Hydrophobity (coefficient in distribution in the hexane water system) and the content of cholinesterase organophosphorous inhibitors (OPI) of the structure Ro (CH3) P (O) SC2H4 SC2H5 were studied in the rat brain. When the O-alkyl radical is increased hydrophobity rises and the relative content of free OPI in the brain extracted by chloroform decreases. With an increase in R from the ethyl to butyl one the ability to the additional inhibition of the brain own cholinesterase lowers due to incubation of homogenate at 37 degrees C, that evidences for an essential drop in the studied series of the free OPI fraction relative to the free OPI extracted by chloroform.

[Microcirculatory changes in poisoning by phosphoorganic cholinesterase inhibitors].

Experiments were conducted on rats and rabbits; a quantitative study was made of the microcirculation, of some indices of gaseous exchange and of the acid-base balance of the blood in poisoning with phosphorus organic cholinesterase inhibitors of peripheral action GA-70. The results obtained were compared and microcirculation disturbances were found to play the leading role in the GA-70-hypoxia developing in intoxication.

[The distribution of cholinesterase charged phosphorganic inhibitors and their uncharged analogues in tissues].

The article deals with the hydrophobic character (distribution coefficient in the systems hexane - water and chloroform - water) and certain peculiarities of distributing three cation-containing phosphoroganic inhibitors of cholinesterase and their uncharged analogues in the organisms. The distribution coefficients in the charged and uncharged compounds in the system hexane - water differ inconsiderably, whereas in the system chloroform-water by the thousands and millions times. In rabbits with intravenous administration the content of all inhibitors in blood decreases rapidly, the uncharged compounds accumulate selectively in the lungs and the charged ones are distributed evenly in the tissues.

[Forms of deposition of phosphoorganic cholinesterase inhibitors in the brain].

The content and hydrophobic properties (distribution coefficient in hexan : water) of organophosphorus inhibitors OPT of the following structure--R-O (CH3)/P/O/S C2H4SC2H5 have been studied in rat brain. On enlargement of the O-alkyl radical from ethyl to isopropyl and pinacolin hydrophobecity increases from 1 to 12 and 39, while the relative content of the chloroform extractable free OPT in brain, under conditions of uniform distribution, decreases from 11--18% to 3.2%.