[Daphnia magna Straus: a test object for the pharmacological evaluation of GABA-ergic drugs in the whole organism].

The toxicity of a series of GABAlytics (11 drugs) representing different pharmacological groups was evaluated in comparative experiments on Daphnia magna Straus and white mice. A high degree of correlation was established between the toxicity of GABA antagonists studied in daphnia and mice. The pharmacological analysis of the interaction of agonists and antagonists of GABA/benzodiazepine/ionophore-receptor complex--the competitive ligands for various binding sites--was carried out. It is suggested that the ability of GABA agonists to prevent the action of GABA antagonists in whole organism is mainly determined by their pharmacokinetic and pharmacodynamic features, rather than by direct competition for binding sites within the receptor complex.

[Daphnia magna for studies of cholinergic preparations]. / Daphnia magna kak ob''ekt pri issledovanii preparatov kholinergicheskogo tipa deistviia.

Published data and original experimental results are summarized to justify biochemically the use of Daphnia magna Straus as an additional or alternative test object for the study of cholinotropic substances. The data of radioligand analysis provide direct evidence that the organism of Daphnia contains M-cholinoreceptors identical (with respect to pharmacodynamic parameters) to those in the human and animal organism.

[New approaches to analysis of the interrelationship between cholinergic and dopaminergic mediator systems]. / Novye podkhody k analizu vzaimootnoshenii kholinergicheskoi i dofaminergicheskoi mediatornykh sistem.

Intermediatory relationships between the cholinergic and dopaminergic neurotransmission systems were analyzed using published data and the original experimental results obtained on Daphnia magna Straus, a new test object. Based on these results, the antihaloperidol activity of a series of M- cholinoblocking agents with different receptor selectivities were studied in comparison to the new cholinoblocker pentifin exceeding in the activity the classical antiparkinsonian drugs such as cyclodol, amedin, and norakin.

[The evaluation of the specific activity and side effects of the m-cholinergic blocker pentifin compared to other antiparkinson agents]. / Otsenka spetsificheskoi aktivnosti i pobochnykh éffektov m-kholinoblokatora pentifina v sravnenii s drugimi antiparkinsonicheskimi sredstvami.

Experiments on rodents showed that pentifin, a muscarine antagonist belonging to the group of acetylene amines, possesses a pronounced antiparkinsonian activity. Pentifin is superior in the breadth of therapeutic action and tolerance characteristics to the conventional agents used for Parkinson's disease treatment.

[Characteristics of effects of acetylene amino alcohols M-cholinoreceptor blockers on the dopaminergic system in Daphnia magna]. / Osobennosti mekhanizma deistviia m-kholinoblokatorov iz gruppy atsetilenovykh aminospirtov na dofaminergicheskuiu sistemu Daphnia magna.

Haloperidol and dimethpromide exhibit the properties of dopamine antagonists in the experiments on Daphnia magna Straus (Crustaceae family). Haloperidol, in contrast to dimethpromide, does not significantly influence the toxic effect of apomorphine. It is suggested that acetylene aminoalcohol derivatives are selective ligands for one of the subtypes of dopamine receptors.

[The possibility of using Daphnia magna as an alternative test object for evaluating the receptor selectivity of cholinotropic substances]. / Vozmozhnost' izpol'zovaniia Daphnia magna v kachestve al'ternativnogo test-ob''ekta dlia otsenki retseptornoi izbiratel'nosti kholinotropnykh veshchestv.

The results of study of the selectivity of the effects of cholinonegative and cholinopositive agents obtained on Daphnia magna hydrobionts were compared with the results of investigations on rats. This allowed Daphnia to be recommended as an alternative test object for studying the selectivity of the effect of cholinotropic agents in relation to some subtypes of muscarine receptors in an intact organism.

[A kinetic study of the blood serum cholinesterase activity in the freshwater fish Abramis ballerus]. / Kineticheskoe issledovanie kholinésteraznoi aktivnosti syvorotki krovi presnovodnoi ryby Abramis ballerus.

In reaction of hydrolysis of choline and thiocholine esters of carbonic acids at 25 degrees C, cholinesterase activity of the blood serum from the fish A. ballerus has been studied by modified Ellman's method and potentiometric titration method. The activity is maximal in pH region 7.5-9.0 and is not inhibited by high concentration of substrates. Michaelis constants and maximal rates for the enzyme reactions were determined. Butyrylcholine and butyrylthiocholine were hydrolyzed with the highest rates by the serum. Some of the organophosphorus inhibitors (diisopropylfluorphosphate and DDVF) inhibit cholinesterase activity of the blood serum significantly faster, whereas some of the carbamates (aminostygmin, eserine, etc.) inhibit it significantly slower than typical butyrylcholinesterase from horse blood serum and typical acetylcholinesterase of human erythrocytes. Besides, with respect to the sensitivity to inhibitors and some other properties, fish blood serum cholinesterase differs from other known cholinesterases.

[The effect of cholinergic substances on the mechanisms of visual recognition in monkeys]. / Vliianie kholinergicheskikh veshchestv na mekhanizmy zritel'nogo uznavaniia u obez'ian.

In monkeys (Macaca mulatta) instrumental reflex was elaborated with differentiation of black-and-white and colour visual stimuli in condition of systemic administration of pharmacological preparations selectively influencing the functional state of cholinergic brain structures. Differentiation of black-and-white and colour stimuli is not disturbed by atropine (0.1 mg/kg) and amizile (up to 1.5 mg/kg) injections; at greater doses frustration of the instrumental reflex takes place. Differentiation of black-and-white and colour stimuli is disturbed at injection of various doses of antidepressant phthoracizine: 5 mg/kg and 7 mg/kg, respectively. These disturbances are restored by the injection of definite doses of galantamine; for correction of colour differentiation a greater dose is required. The obtained data point to differences in neurophysiological and neurochemical processes responsible for black-and-white and colour vision.

[Effect of reversible inhibitors on the reaction capacity of functional portions of the active center of acetylcholinesterase]. / Vliianie obratimykh ingibitorov na reaktsionnuiu sposobnost' funktsional'nykh uchastkov aktivnogo tsentra atsetilkholinésterazy.

The effect of galanthamine, tacrine, and oxazyl (ambenomum) on human red cells acetylcholinesterase phosphorylation by armine and Gd-42 (o-ethyl-s-beta-ethylthioethyl ester of methylthiophosphinic acid) was studied. In the presence of galanthamine phosphororganic inhibitors interacted only with the active center of the enzyme, the anionic site of which was not occupied by the reversible inhibitor. Tacrine and oxazyl decreased the reactivity of the free enzyme and the rate of its phosphorylation.

[Mechanism of the effect of diazepam on acetylcholine concentration in mouse brain]. / Issledovanie mekhanizma vliianiia diazepama na soderzhanie atsetilkholina v golovnom mozge myshei.

Intraperitoneal injection of diazepam (20 mg/kg) caused an increase of free and bound acetylcholine in the mouse brain. Diazepam pretreatment (20 mg/kg) increased galanthamine anticholinesterase activity and its toxicity; as to physostigmine, armine, and paraoxon toxicity--it remained unchanged. It is supposed that diazepam blocks the release of aetylcholine from the cholinergic nerve terminals which should result in a decrease of functional acetylcholine concentrations in the synapse.

[Interaction of reversible inhibitors with the catalytic centers and allosteric sites of cholinesterases]. / Vzaimodeistvie obratimykh ingibitorov s kataliticheskimi tsentrami i allostericheskimi uchastkami kholiénsteraz

The kinetics of inhibition of the human red blood cell cholinesterase with galanthamine tacrine and oxazyl (ambenonium) and the effect of these drugs on chick, mouse, cat and rat blood plasma enzyme activity was studied. Galanthamine proved to bind with acetylcholinesterase in the anionic areas of the catalytic centres, oxazyl interacted in the area of the allosteric anionic site, and tacrin interacted with the hydrophobic areas of the enzyme.

[Galanthamine interaction with mouse brain acetylcholinesterase in in vivo experiments]. / Izuchenie osobennostei vzaimodeistviia galantamina s atsetilkholinésterazoi mozga v opytakh in vivo

Armine treatment of mice against the background of preliminary galanthamine injection diminished the inhibition of the acetylcholinesterase of the brain caused by a reversible inhibitor. This effect was connected with the acetylcholine accumulation and the displacement by it of galanthamine from the active centres of the enzyme. Thus, a competitive character of galanthamine-acetylcholinesterase interaction was shown in vivo.

[Comparison of anticholinesterase activity and the effectiveness of anticholinesterase substances]. / Sopostavlenie antikholinesteraznoi aktivnosti i effektivnosti antikholinesteraznykh sredstv

In vitro tests set up to compare the anticholinesterase, cholinomimetic, cholinopotentiating and cholinolytic activity of 6 reversible cholinesterase inhibitors furnished grounds for an inference that all these agents produce an anticholinesterase effect which determines the qualitative specificity of their action. This specificity has been demonstrated in experiments on cats and rabbits. Some of the drugs (oxazyl) exert a practically elective effect on the H-cholinoreactive muscle systems, whereas others (eserin) act in a similar manner on the M-cholinoreactive systems of the intestines. The action of proserine and galanthamine os of a less selective nature.

[Effect of reversible inhibitors on the thermal denaturation of cholinesterases]. / Vliianie obratimykh ingibitorov na teplovuiu denaturatsiiu kholinésteraz

The capacity of reversible inhibitors--galanthamine and tacrine--to protect the cholinesterase of rat and mouse brain from the thermal denaturation with the action of the temperature of 56 and 58 degrees C was revealed. The protective action was also noted when the reversible inhibitors decreased the activity of the enzyme. It appeared that with galanthamine the cholinesterase resistance to the thermal action was greater than with the action of tacrine.

[Mechanism of the hypothermic action of reversible cholinesterase inhibitors]. / K mekhanizm gipotermicheskogo deitviia obratimykh ingibitorov kholinésterazy

Experiments set up on mice demonstrated that galanthamine, hydrobromide, physostymine salicilate and iodomethylate produce a fall of the renal temperature, the hypothermal effect being proportional to the suppression of the cerebral cholinesterase. Anticholinergics benactyzine and atropine were largely capable of preventing hypothermia produced by the introduction of galathamine hydrobromide, the latter increasing the resistance of the animals to the action of high temperature.

[Effect of 1,4-benzodiazepine derivatives on the toxic action of oxygen under increased pressure]. / Vliianie proizvodnykh 1,4-benzodiazepina na toksicheskoe deistvie kisloroda pod povyshennym davleniem

The 1,4-benzodiazepine derivatives (diazepam, nitrazepm, lorazepam, clonazepam and two newly synthetized compounds of this series) increase the resistance of albino rats and rabbits to the toxic effect of oxygen under high pressure (7 and 5.5 atm respectively). The compounds under study are apt to avert over a long period the development of metabolic acidosis which appears following the action of high-pressure oxygen on the body.