[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. Caffeine (a nonselective antagonist of adenosine receptors) potentiates the action of carbamylcholine during the first hour and then ceases to influence the drug effect. Caffeine normalizes the HR rate D magna, which was decreased by the cholinolytic atropine and the beta-adrenolytic atenolol. The possibilities of using the proposed test for the investigation of intermediatory relationships in the HR regulation, rapid analysis of the cardiothropic action of xenobiotics, and the primary screening of drugs for the pharmacological correction of HR disturbances are discussed.

[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). Plots of the real time of daphnia death versus MPTP concentration are presented and the concentration limits of its specific activity are evaluated. Experiments on daphnia under the conditions of MPTP intoxication were used to study the modulating effects of drugs producing a pharmacological correction of dopamine secretion disturbances in mammals. It is shown that the exogenous dopamine, muscarinic cholinoblocker pentifine, and antioxidant unithiol exhibit a protective action. Reduced glutathione does not possess protective properties. It is suggested to use D. magna as a simple and informative test object for the modeling of dopaminergic transmission deficiency and for the primary screening of various substances intended for the pharmacological correction of dopamine transmission disturbances.

[Fluoride tolerance in cases of dental caries and fluorosis].

32 volunteers (18-20-year-olds) without concomitant diseases were divided into 3 groups: with high caries incidence (1), with dental fluorosis of different degrees (2) and with completely intact dentition (3). Dynamics of ionized F in blood serum and mixed saliva after single sodium fluoride burden (F-dosage=0.1 mg/kg body weight) was determined 1, 2, 3, 5, 7 and 24 hours after per os consumption by Orion-9609-BN F-selective electrode. F bound by organic material was assayed after breaking covalent bond C-F by sodium diphenyl. It was common for all participants that wide range of sensitivity to ingested F but F-tolerance had reversed trends in caries and fluorosis. Content of organic "fluoride" in blood serum changed insignificantly. In mixed saliva the dynamics of ionized F in dental caries and fluorosis conditions followed to some extent blood serum trends.

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.

[Effect of M3-choline receptor blockade on the ability of muscarinic antagonists to prevent catalepsy induced by haloperidol in rats]. / Vliianie blokady M3-kholinoretseptorov na sposobnost' muskarinovykh antagonistov preduprezhdat' katalepsiiu, vyzvannuiu galoperidolom u krys.

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. It is suggested that the high antihaloperidol activity of pentiphine (an acetyleneamine alcohol) is explained by its dopaminomimetic properties rather than by the anticholinergic activity.

[The role of the blockade of separate subtypes of muscarinic receptors in realizing the antidotal effect of m-cholinolytics in dimethyl dichlorovinyl phosphate poisoning]. / Rol' blokady otdel'nykh podstipov muskarinovykh retseptorov v osushchestvlenii antidotnogo éffekta m-kholinolitikov pri otravlenii dimetildikhklorvinilfosfatom.

On comparison of the values of receptor selectivity of a series of m-cholinoblockers in vitro with those of the selectivity of their effect in in vivo experiments, pharmacological tests characterizing the interaction of ligands with m1, m2, and m3-subtypes of muscarine receptors were determined. Analysis of the protective effect of m-cholinoblockers in poisoning with organophosphorus compounds (OPC) depending on their activity in the determined tests showed that blocking of the m1-cholinoceptors is responsible for the antidotal effect of the antagonists, whereas block ing of m2-cholinoceptors prevents it. It is suggested that the negative effect of m2-cholinoceptor blocking on the protective effect of the drugs in OPC poisoning is mediate d by increased excretion of the mediator into the synaptic cleft as a result of interaction of the ligands with the presynaptic autochol inoceptors.

[The antiparkinson activity of muscarinic antagonists depending on their selectivity for individual m-cholinoreceptor subtypes]. / Antiparkinsonicheskaia aktivnost' muskarinovykh antagonistov v zavisimosti ot ikh izbiratel'nosti k otdel'nym podtipam m-kholinoretseptorov.

The dependence between the activity parameters of muscarine antagonists in the prevention of haloperidol catalepsy in rats and those in tests characterizing the interaction of ligands and various subtypes of m-cholinoceptors was studied. It was established by constructing the mathematical dependence that blockade of m1-cholinoceptors increases, while that of m2-cholinoceptors reduces the antiparkinsonian activity of the drugs. The activity of the muscarine antagonist pentiphan in the prevention of haloperidol-induced catalepsy in rats exceeds the activity of such traditional antiparkinsonian drugs as cyclodol and amedin.