[Studying intermediatory regulation of heart rhythm using Daphnia magna as the alternative test object].

A functional test using Daphnia magna Straus hydrobionts is proposed for studying the role of intermediatory relationships in the heart rate (HR) regulation. It is established that the M-cholinomimetic carbamylcholine increases for two hours and decreases after 24 hours the HR in D. magna.

[Heart rate in Daphnia magna as a functional test for assessing efficacy of chemical agents].

It is suggested to use Daphnia magna Straus as a biotest object for the evaluation of heart rate (HR) as a functional parameter. The influence of cholinergic ligands (atropine and carbamylcholine) on the Daphnia cardiac rhythm has been studied. It is found that the cholinergic agonist and antagonist produced opposite influence on the HR and are capable of prevent the action of each other.

[Daphnia magna (straus): a new test object for modeling of dopaminergic neurotransmission deficiency induced by the selective neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine].

The possibility of using Daphnia magna (Straus) hydrobionts as a test object in modeling the disturbances of dopaminergic neurotransmission was investigated. The toxic action of a selective dopaminergic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), on D. magna was determined in a broad interval of concentrations (from 2 x 10(-5) to 10(-2) M).

[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.

[Daphnia magna Straus: a new model for evaluating the antioxidant acton of water-soluble preparations in vivo].

Hydrobionta species of Daphnia magna Straus were used as a test objects for in vivo evaluation of the antioxidant activity of three hydrophilic thiol compounds: reduced gluthatione, unithiol, and cysteine. These compounds exhibited significant differences in activity under oxidative stress conditions, in the dynamics of observed effects, and in the probability of inversion from anti- to pro-oxidant action. The main advantage of the proposed test objects in comparison to the conventional in vitro experiments (where the antioxidant effect is evaluated over a period of time from several minutes to several hours) is that the development of drug activity (pro- and antioxidant effects) can be monitored over a prolonged period of time (up to several days).

Effect of M2 muscarinic receptor blockade in rats with haloperidol-produced catatonic syndrome.

We studied the functional role of individual subtypes of muscarinic cholinoceptors in the pathogenesis of neuroleptic parkinsonism in rats. Blockade of M4 receptors prevented the development of extrapyramidal disorders, which was abolished by simultaneous blockade of M2 receptors. The data suggest that various subtypes of muscarinic receptors are involved in the regulation of dopamine concentration.

Effects of cholinoblockers on acetylcholine content in rat striatum in neuroleptic-induced parkinsonism.

Correction of neuroleptic-induced parkinsonism in rats with two central cholinoblockers atropine and pentifine (acetylene aminoalcohol synthesized at Institute of Toxicology) were studied by measuring the content of acetylcholine in the striatum. The content of the transmitter secretion was estimated from the content of bound acetylcholine fraction in homogenates of the above-mentioned compartment of the brain. The results indicate that atropine and pentifine in doses equally effectively preventing catalepsy in rats had different effects on acetylcholine secretion in the striatum.

Effect of M4-cholinoceptor blockade on haloperidol-produced catatonic syndrome in rats.

We studied the relationship between the efficiency of muscarinic receptor antagonists in preventing haloperidol-induced catatonia and their activity in tests for the interaction of ligands with various subtypes of muscarinic receptors (M1-M4) in rats. Mathematical modeling showed that affinity of the ligand for M4 receptors positively affects its ability to correct extrapyramidal disorders (catatonic syndrome) produced by haloperidol, while affinity for M2 receptors had a negative effect on this characteristic.

[Differences in prooxidant effect of neuroleptics haloperidol and aminazine].

In the in vitro experiments with hydrobiont Daphnia magna Straus as the test-object the comparative evaluation of the prooxydant activity of two neuroleptics galoperidol and aminazine, was performed. It was shown that galoperidol possesses the pronounced prooxydant activity compared with hydrogen peroxyde. Aminazine didn't display such an action.

In vitro effects of pentifin on some neurotransmitter systems in the brain.

Pentifin and dopamine D1 receptor antagonist SCH-23390 possess similar pharmacological properties. In the present work we studied in vitro effects of Pentifin on dopamine receptors. Experiments on rat ductus deferents showed that Pentifin acts as a weak ligand of dopamine receptors.

Qualitative assessment of selective blockade of M(4)-cholinoreceptors in the whole organism.

Quantitative assessment of selective blockade of M4-subtype muscarinic receptors was performed by the number of pilocarpine-induced movements of lower jaw in rats. Three antagonists (atropine, cyclodol, and glipin) were used in the experiments. Glipin produced the most potent blockade of M4 receptors in the whole organism compared to other test antagonist.

[Pharmacological analysis of the pathogenesis of acute poisoning with the synthetic pyrethroid cypermethrin using the hydrobiont Daphnia magna Straus].

The results of pharmacological analysis are presented which provide information on the pathogenesis of acute cypermethrin poisoning that involves disturbances in various systems of the organism. These include changes in the system of excitatory amino acids (EAAs) and violation of the free radical generation processes, Na + channel functioning, cholinergic transmission, etc. The screening of drugs belonging to various pharmacological groups influencing the toxicity of pyrethroids (EAA receptor antagonists, antioxidants, Na + channel blockers, M-cholinoreceptor blockers) revealed promising agents for the treatment of cypermethrin poisoning.

Mathematical analysis of subtypes of muscarinic receptors modulating heart and respiratory rhythms in rats.

Mathematical analysis of the data obtained in experiments on the whole organism revealed that blockade of M(2)-cholinergic receptors increased both heart and respiratory rates. Blockade of M(1)-cholinergic receptors alleviated tachycardia induced by M(2)-receptor blockade.

[Daphnia magna for studies of cholinergic preparations].

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].

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.

[Effect of M3-choline receptor blockade on the ability of muscarinic antagonists to prevent catalepsy induced by haloperidol in rats].

A relationship between the indices of efficacy of the muscarinic antagonists in preventing the haloperidol catalepsy and their activity in the tests characterizing the interaction of these ligands with various subtypes of m-cholinoreceptors was studied in rats. A mathematical model was formulated that confirmed the previous conclusion concerning the role of of the m1- and m2-cholinoreceptor blockade in the antiparkinsonian activity of muscarinic antagonists. It was established that blocking of the m3-cholinoreceptors decreases the anticataleptic activity of m-cholinoblockers with respect to haloperidol.

[Characteristics of effects of acetylene amino alcohols M-cholinoreceptor blockers on the dopaminergic system in 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.

[Subtypes and neuronal localization of muscarinic receptors in rat cerebral hemispheres].

The subtypes of pre- and postsynaptic muscarinic receptors in rat cerebral hemispheres were determined using a new approach based on the radioligand analysis.

[The role of adenylate cyclase and phosphoinositide second messenger systems in regulation of acetylcholine secretion in synapses of the cerebral hemispheres and brain stem in rats].

Changes in acetylcholine secretion in the cholinergic synapses of the rat cerebral hemispheres and brain stem were studied in in vivo experiments against the background of modulation of the activity of the adenylate cyclase and phosphoinositide secondary messenger systems by injection of caffeine and lithium chloride. The level of mediator secretion was determined according to the content of bound acetylcholine fractions in the homogenate of the indicated parts of the animal's brain. It was established that secretion of the mediator in the rat hemispheres is regulated by postsynaptic N-cholinoceptors located on the body of cholinergic neurons which have a phosphoinositide system actiung as secondary mediators and, possibly are related to subtype M1.

[The presynaptic mechanism of interaction of cholinesterase reactivator and muscarinic antagonists in the animal's defence in organophosphate intoxication].

The presynaptic and antidote activity of various combinations of cholinesterase reactivators and that of muscarinic antagonist were compare it was show that the mechanism of the antidote effect of some cholinesterase reactivators in poisoning with organophosphorous compounds, in addition to restoring the activity of the enzyme, includes the effect of counteraction to the effect of muscarinic antagonists in increased acetylcholine secretion into the synaptic cleft. The expression of this effect depends on the presynaptic activity of the reactivator and on the selectivity of muscarinic antagonist. It is suggested that the type relation of the presynaptic muscarin receptors in the cerebral hemispheres and the brain stem is different and that the probability of the functional value of the ligand presynaptic interaction for the protection from organophosphorous compounds is higher in the brain higher in the brain stem than in the cerebral hemispheres of rats.

[The role of the muscarinic receptors in the pathogenesis of the convulsive state induced by korazol in rats].

It was established in experiments on albino rats that blockade of the muscarinic receptors by various M-cholinolytics reduces the dose of corazol necessary for the development of a convulsive state. Preliminary administration of some cholinopositive agents raises the corazol action threshold. It is suggested on the basis of pharmacological analysis that the role of the cholinergic system in the pathogenesis of corasol-induced convulsive state in rats is mediated by the function of cholinoreceptors related to subtype M4 or M1.

[New approaches to determining the type classification of presynaptic acetylcholine receptors].

A complex of special tests which took into account the coupling of the specific physiological responses with individual subtypes of muscarinic cholinoceptors, and radioligand analysis showed the predominance of M3- and M2-subtype presynaptic receptors in the rat brain hemispheres. The autoreceptors regulating the presynaptic release of acetylcholine are related mainly to the M2-subtype and account for the smaller part of the mixed population of presynaptic receptors.