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The new cholinesterase reactivator alloxime, 10 mg/kg, shows a marked therapeutical benefits in acute intoxication rats with carbamine pesticides such as carbofuran, pirimor, elocron. The therapy of alloxime in combination with atropine, 10 mg/kg, results to their combined therapeutical effect, the toxicity of carbofuran, elocron, and pirimor (by LD50) decreasing by 8.4, 5.6, and 3.5 times, respectively). The mechanism of alloxime's therapeutical action is due to its capacity to restore cholinesterase activity in the central nervous system, normalizing neuromuscular transmission and hepatic and renal cytochrome P-450 levels.

It has been established that administration of aphos to chickens within a wide dose range (3000-25 mg/kg) produces a retarded neurotoxic action that is manifested by the development of ataxia, pareses and paralyses; delay in the rate of the distribution of excitation via the peripheral axons, disorders of myoneural lability; degeneration of myelin fibers, focal granular degradation of myelin. The retarded neurotoxic action is not caused by impurities contained by the technical-grade preparation in view of the fact that such an action is also common to the chemically pure aphos.

The inhibition of neurotoxic esterase activity in chicken brain has been studied in vitro and in vivo. Aphos exposure, causing chicken paralysis, has demonstrated that the initial stage of delayed neurotoxicity was significant esterase activity inhibition (by 60-80%) within 3-24 hours after the pesticide administration. The inhibition of cholinesterase activity occurred both in the blood and sciatic nerve. The delayed conduction through peripheral nerves caused by demyelination has been revealed in the latent period (before the clinical signs of intoxication).

A new cholinesteras reactivator--chlorohydrate of S-diethylaminoethyl ether p-bromo benzoylthiohydroxime acid (diethixime), containing a tertiary nitrogen atom in the molecule, was shown to produce a central effect in a dose of 20 mg/kg--1/50 LD50--in contrast to diproxime in a dose of 3 mg/kg, containing a quarternary nitrogen atom, under intoxication of albino rats and rabbits with dimethyl-dichlorynylphosphate. This effect was confirmed by the restortion of the cholinesterase activity in different parts of the rabbit brain, by the normalization of the EEGand of the functional stateof motor neurons of the rat spinal cord.

Experimental data on the effectiveness of p-brombenzothiohydroximic S-diethylaminoethylate (diethyxime) -a new cholinesterase reactivator - are presented. The diethyximetoxicity with its single and multiple administration to animals was studied. The drug is shown to display a marked antidotal action when used in a dosage range of 490-10 mg/kg. Diethyxime is shown capable of restoring the activity of cholinesterase inhibited by dimethyldichlorovenylphosphate, of preventing the neuro-muscular block of the impulses conduction and of normalizing the function of the cardiovascular system. The drug is less toxic than is presently employed reactivator diproxime and it does not produce any side-effects on a number of organs and systems of the organism with its multiple administration to worm-blooded animals.

It was shown on a model of intoxication of hens with aphos possessing a selective neuroparalytic action that the target-enzyme neurotoxic esterase changed its activity in the brain, spleen and lymphocytes of the peripheral blood. The authors describe a method of determination of the activity of neurotoxic esterase in human peripheral blood lymphocytes that may be used for biomonitoring of the effect of phosphorus organic compounds possessing a delayed neurotoxic action.

Unlike dipyroxime (10 mg/kg), a new cholinesterase reactivator diethyxime (20 mg/kg) exerts a therapeutic action in acute poisoning of rats with carbamine pesticides (carbofuran, elocron, pirimor, croneton). Therapy with diethyxime combined with atropine (at a rate of 10 mg/kg) leads to the summation of therapeutic effects. At the same time the toxicity of carbofuran, pirimor, croneton and elocron as regards the LD50 decreases 8.75-fold, 5.4-, 4- and 2,84-fold, respectively. The mechanism of the therapeutic action of diethyxime is determined by its capacity to recover cholinesterase activity both in the peripheral and central nervous systems, as well as to normalize neuromuscular transmission. It is necessary to take into account the cholinolytic effect displayed by diethyxime.

The inductor of microsomal enzymes, benzonal (20 mg/kg) produces an overt preventive and treatment-preventive action in acute and subacute poisoning with organophosphorus (DDVP, parathion, TEPP, chlorophos) and carbamic (pirimor, sevin) compounds. As regards the efficacy benzonal is not inferior to phenobarbital (14 mg/kg). Pretreatment with benzonal averts the development of the neuromuscular blockade and normalizes spontaneous activity of the myoneural synapse of rats and cats poisoned with pirimor and parathion.

Zyxorin (50-100 mg/kg) was found to produce a significant increase of the content (activity) of components of electron transport microsomal circuit and is similar to phenobarbital by its inducing effect. At preventive and therapeutic-preventive administration it enhances resistance of albino rats to anticholinesterase pesticides (actellis, valexon, 0,0-dimethyl-0-2,2-dichlorvinylphosphate, clorofos, hostaquick, dioxycarb, primor, sevine, furadan), prevents the development of neuromuscular blockade. The introduction of zyxorin into a complex therapy with specific agents (atropine, reactivators of cholinesterase) potentiates their antidotic effect at poisoning with DDVP.