[Hypolipidemic activity of N-cholinergic antagonist Benzohexonium in the experiments ].

Methods: Experiments were carried out on outbred albino male rats (n = 150, 230-250 g). For modeling dislipoproteinemia (DLP) we used 3 models: single intraperitoneal injection of the detergent triton WR-1339; administration of ethanol; maintenance on a special hypercholesterolaemic diet (HD) during 21 days. Animals were divided into four groups: normal control, model group, gemfibrozil (Gfb) group, benzohexonium (Benz) group. Rats received per os benzohexonium (20mg/kg), reference drug gemfibrozil (50 mg/kg). We determined content of total cholesterol (TCh), triglycerides (TG) in samples of blood serum and liver, TCh in aorta. TCh, TG and Ch-HDL were analyzed spectrophotometrically using of standardized methods. Results: Compared with model group the contents of TCh, TG in serum and liver were significantly decreased in model + Benz group, whereas Ch-HDL was raised in rats fed special HD (P<0.05). Calculated index of atherogenity (TCh - Ch-HDL) / (Ch-HDL) showed the positive effect. Conclusion: The results obtained were shown the hypolipidemic activity of N-cholinergic antagonist Benzohexonium (20 mg/kg) lowered the content of lipids in blood, liver, and aorta.

A new activity of N-cholinolytic drug benzohexonium.

We have found that N-cholinolytic drug benzohexonium produces a hypolipidemic effect: it reduces dyslipoproteinemia, fatty infiltration of the liver, and risk of atherosclerotic lesions.

[Combined use of reminyl (galanthamine) and ovestin (oestradiol) for the treatment of cognitive disorders in women with hypoestrogenic syndrome].

The efficacy of a combined therapy with reminyl and ovestin in low doses used for pharmacocorrection of cognitive disorders in women after total ovariectomy has been studied. The results show a pronounced efficacy of the proposed combined therapy as compared to the standard hormonal replacement therapy in women with hypoestrogenic syndrome, which is confirmed by a significant decrease in the expression of mental impairments evaluated using the BCRS, CCSE, and MMSE methods.

[Effects of cholinergic antagonists in stress].

Effects of methacine, hexamethonium and their combinations with neostigmine on activity of B-lymphocytes in various phases of immune response and development of stress ulcers induced in animals were studied. The drugs were found to modulate B-lymphocyte activity for 28 days and longer. By a water-immersion stress model it was shown that methacin is effective not only as m-cholinolytic but also as an immunoprophylactic drug reducing destructive changes in gastric mucosa. Injection of methacin 30 min before stress (block of m-cholinoreceptors) or 14 days before stress (maximal increase of B cell activity) results in 3-4-fold inhibition of ulcerogenesis in gastric mucosa.

[Possibilities of controlling intraoperative thermoregulation].

The agents containing succinic and fumaric acids were used to control body temperature during an operation. Elective surgical interventions into small pelvic organs were made in 22 females aged 28-55 years, who were divided into 2 groups. In group 1 (n = 11), the agents containing succinic and fumaric acids were used and infusion therapy that did not differ from Group 2 (n = 11) in all other respects. The level of metabolism, temperature in the rectum and big toe, and other parameters were estimated. Administration of the drugs containing carboxylic acids of the Krebs cycle was shown to lead to the activatization of metabolism, the maintenance of core temperature, by increasing peripheral body temperature at surgery.

[Optimizing effect of the combined administration of 8-OH-DPAT and galantamine on depression--anxiety behavior in old rats with dementia of Alzheimer's type].

The effect of chronic (14 days) administration of the serotonin 5-HT(1A) receptors agonist 8-OH-DPAT (0.05 mg/kg, s.c.) and the 5-HT(1A) receptors antagonist NAN-190 (0.1 mg/kg, i.p.) alone or in combination with the acetylcholinesterase inhibitor galantamine (1.0 mg/kg, i.p.) on depression and anxiety was studied in old (24 months) male rats with dementia of Alzheimer's type. The results indicated that chronic combined administration of 8-OH-DPAT with galantamine resulted in pronounced antidepressant and anxiolytic action.

[The cholinergic system of lymphocytes].

The role of acetylcholine and the cholinergic system in non-neuronal cells (in particular, in lymphocytes) in humans is considered. Lymphocytes express most of the cholinergic components found in the nervous system, which makes possible acetylcholine-dependent stimulation of lymphocytes in the spleen and lymph nodes. The sympathetic innervation and paracrine mediators control several immune cell functions, the blood perfusion, lymphoid cells and antigen uptake by the lymphoid organs. Cholinergic compounds can influence the immune system through the CNS (via hypothalamic - pituitary - adrenal axis), the autonomoic nervous system, and/or an independent non-neuronal cholinergic system in lymphocytes. The dysfunction of the non-neuronal cholinergic system plays a certain role in the pathogenesis of many diseases. Experiments revealed the possibility to modulate some effects of non-neuronal acetylcholine in the prevention of stress-induced ulcers and anaphylactic shock. This could provide a basis for the development of new therapeutic strategies to target the non-neuronal cholinergic system.

[Effect of some imidazole-4,5-dicarboxylic acid derivatives on the activity of N-methyl-D-aspartate (NMDA) receptors].

The results of experiments on mice showed that some imidazole-4,5-dicarboxylic acid derivatives injected into lateral cerebral ventricles produce a dose-dependent convulsant or anticonvulsant effects, that is, possess the properties of partial NMDA receptor agonists. The most promising partial NMDA receptor agonist selected for further investigation is 2-propylimidazole-4,5-dicarboxylic acid.

[Effect of acetylcholine and C-reactive protein on regulation of anaphylactic shock in guinea pigs].

The investigation of acetylcholine-dependent regulation of the model anaphylaxic shock in guinea pigs showed that an increase in the concentration of endogenous acetylcholine in sensitized animals leads to an increase in the agonal shock period (by 15 +/- 1 min in the test and 3 +/- 1 min in the control) and abolishes shock in the pathochemical phase: anaphylactic index 0.4 +/- 0.02 in the test against 4 +/- 0.02 in the control). The injection of purified blood plasma proteins-IgG or C-reactive protein (CRP) preparations--decreased the anaphylactic reaction. The activation of cholinergic tone prior to shock induction is an effective means of preventing shock development. The acquired resistance decreased the response to repeated injections of horse serum. Animals protected from the shock (methacin 40 min and neostigmine 15 min prior to shock, or methacine plus IgG 40 min prior to shock) showed nearly normal PFCs. The effect of methacin was significantly influenced by simultaneously injected plasma proteins: IgG potentiated the broncholytic effect of methacin, while CRP abrogated it. The effective antishock therapy led to normalization of the antibody production activity of B-lymphocytes, while unprotected animals exhibited increased level of antibody production.

Characteristics of cholinoreceptors on identified TAN neurons of the ground snail Achatina fulica.

The characteristics of cholinoreceptors located on neurons TAN1, TAN2, and TAN3 of the ground snail Achatina fulica were studied by incubation of the central ganglia in a bath with cholinotropic preparations during intracellular recording of background neuron spike activity. Acetylcholine, nicotine, the selective n-cholinoreceptor agonist suberyldicholine, and the selective n-cholinoreceptor agonist 5-methylfurmethide concentration-dependently inhibited background spike activity to the level of complete blockade at concentrations of 500 microM. The m-cholinoblocker metamizil (500 microM) completely prevented the inhibitory activity of concentrations of 5-methylfurmethide of up to 500 microM. The central n-cholinoblocker etherophen (500 microM) completely blocked the inhibitory activity of 500 microM suberyldicholine. However, metamizil and etherophen added separately only partially decreased the inhibitory effects of acetylcholine but could not completely block the effect of acetylcholine. At the same time, mixtures of metamizil and etherophen (500 microM each) completely blocked the inhibition of background spike activity induced by acetylcholine. These results show that both classes of cholinoreceptors act on TAN neurons in the same direction.

[Role of M- and N-cholinergic systems in the recovery of motor functions after removal of the motor zones of the cerebral cortex in cats]. / Rol' M- i N-kholinergicheskikh sistem v vosstanovlenii dvigatel'nykh funktsii posle udaleniia motornykh zon kory bol'shikh polusharii u koshek.

In chronic experiments on cats with unilateral ablations of the motor cortical area, recovery of motor function of the contralateral forelimb was observed in average on the 31-th day after ablation. Stimulation of M-cholinoreactive brain biosystems by galantamine in combination with simultaneous suppression of N-cholinoreactive biosystems by ganglerone, shortened the period of complete compesation up to 10 days. Suppression of M-cholinoreactive systems and simultaneous stimulation of N-cholinoreactive ones by metamisil combined with galantamine prolonged the recovery period up to several months. A conclusion is drawn of an important role of M- and N-cholinergic mechanisms in providing compensatory possibilities of the brain.

[Method of treating parkinsonism with metamizil in combination with galanthamine (clinico-experimental basis)]. / Sposob lecheniia parkinsonizma metamizilom v sochetanii s galantaminom (kliniko-eksperimental'noe obosnovanie).

Using experimental models of parkinsonism, imitating the hypertonus of the parasympathetic system (hypokinesia, rigidity and tremor) following the intraperitoneal injection of the acetylcholinesterase inhibitor galanthamin (15 mg/kg) to mice, the authors showed that the m-cholinoblocker metamisyl (2 mg/kg) blocks all manifestations of the CNS parasympathetic hypertonus whereas the n-cholinoblocker eterofen (30 mg/kg) increases them. Based on the theory developed by the authors as to the reciprocity of interaction between the m- and n-cholinergic mechanisms within the framework of the single cholinergic system of the body, they offered the treatment of parkinsonism by the combined use of metamisyl (1-2 mg) and galanthamin (5-10 mg). Forty-five patients were treated with metamisyl alone and 40 patients with metamisyl coupled with galanthamin. The latter method of treatment proved to be more effective. The patients responded to the treatment immediately. It lasted 2-4 weeks. The follow-up showed that in some patients, the effect of the treatment stabilized and persisted for 4 weeks to 12 months without the use of the antiparkinsonian drugs. The authors emphasize that in cases of parkinsonism it is necessary to study and take into account the nature of changes in both intersystemic mediator interaction (between ACh and NA, ACh and D, ACh and 5-HT, etc.) and the intrasystemic one (between m- and n-cholino, alpha- and beta-adreno, D1 and D2, 5-HT1 and 5-HT2-ergic mechanisms).

[Distribution and functional characteristics of N- and M-cholinoreceptors in structures of the striopallidal complex]. / O raspredelenii i funktsional'noi kharakteristike N- i M-kholinoretseptorov v strukturakh striopallidarnogo kompleksa.

Microapplication of arecoline, nicotine, methamizil, and beta-ethydiphazil in unanesthetized immobilized rabbits through chemotrodes implanted into the head of nucleus caudatus, putamen, globus pallidus, hippocampus, reticular formation and frontal cortex revealed inhibitory and activating effects of arecoline and nicotine. Specific antagonism between the effects of M- and N-cholinomimetics and between corresponding M- and N-cholinoblockers, was shown. Existence of M- and N-cholinoreactive biochemical systems with reciprocal relations is supposed in different zones of the striatum.

[Role of M- and N-cholinergic biosystems of the brain in the mechanisms responsible for optokinetic, postoptokinetic, and reversed postoptokinetic nystagmus]. / Rol' M- i N-kholinergicheskikh biosistem mozga v mekhanizmakh formirovaniia optokineticheskogo, postoptokineticheskogo i reversivnogo postoptokineticheskogo nistagmov.

In rabbits, the effects of different inhibitors: of Achesterase--nivalin, of M-cholinergic receptors--metamizyl and N-cholinergic receptor--eterophen on the optokinetic nystagmus (OKN), positive optokinetic afternystagmus (OKAN) and reversed postoptokinetic nystagmus (RPN) revealed that in mechanism of the OKH, OKAN and RPN both colinergic systems took part: N-cholinergic system in the OKH and OKAN and M-cholinergic system in RPN formation.

[The effect of cholinergic-potentiating and cholinergic-blocking agents on reparative processes in the damaged gastric mucosa of rats]. / Vliianie kholinopotentsiruiushchikh i kholinoblokiruiushchikh sredstv na reparativnye protsessy v povrezhdennoi slizistoi obolochki zheludka krys.

Rat experiments have indicated that increased lipid peroxidation in gastric tissue occurs with formation of cryogenic gastric ulcers. The use of methacin alone, 1 mg/kg i.p., and in combination with proserinum, 0.1 mg/kg, s.c., metamisyl alone, 1 mg/kg, i. p., and in combination with galanthamine hydrobromide, 1 mg/kg, s. c., result in acceleration of reparative process in the rat gastric walls and normalization of gastric tissue malonic dialdehyde levels. Methacin in combination with proserinum has been found to be most beneficial.

[Effect of etimizol on the nystagmic reactions in optokinetic stimulation and aftereffect]. / Vliianie étimizola na nistagmennye reaktsii v period optokineti-cheskoi stimuliatsii i v posledeistvii.

In chronic experiments on rabbits, changes of frequency and amplitude of the optokinetic nystagmus (OKN) were studied during continuous 60-min optokinetic (OK) stimulation and in secondary trace reverse phase of the OKN called the reverse postoptokinetic nystagmus (RPN) for 30 min after cessation of the OK-stimulation prior to and after administration of 5 mg/kg aethimizol. The drug was administered 20 min prior to the OK-stimulation and on the 35th min of the stimulation. Aethimizol was found to increase considerably the OKN frequency, amplitude and the RPN. The RPN frequency was considerably decreased after aethimizol administration. Aethimizol seems to improve the process of nystagmus formation during the OK-stimulation and to weaken the process of formation of the asymmetry of nervous centers excitation during a prolonged OK-stimulation.

[Functional significance of alpha- and beta-adrenoreceptors in structures of the stropallidal system]. / O funktsional'nom znachenii alpha- i beta-adrenoretseptorov v strukturakh striopallidarnoi sistemy

Microapplication of noradrenaline, isadrine, phentolamine, and propranole to neuroanal populations of the striatum in curarized unanesthetized rabbits revealed an inhibitory and stimulatory effects of noradrenaline and isadrine. A specific antagonism between alpha- and beta-adrenomimetics and respective alpha- and beta-adrenoblocking agents, was noted. Noradenaline seems to have a very important mediatory function in the adrenergic synapases of the striatum. Existence of alpha- and beta-adrenoreceptors with different functions in different brain areas, is suggested.

[Effect of etimizol, ethyrasol, and caffeine on the electrical activity of mollusk neurons]. / Vliianie étimizola, étirazola i kofeina na élektricheskuiu aktivnost' neironov molliuskov.

In experiments on Limnae stagnalis neurons, ethymisol increased the AP duration while reducing the trace hyperpolarization and the rate of development of the AP descending phase. Ethymisol (10 mM/1) induced either hyperpolarization of neurons with an increase in membrane resistance or their depolarization (20 mM/1) with a decrease in membrane resistance. A drop in the medium temperature by 2-4 degrees C prevented the hyperpolarization. The ethymisol-induced hyperpolarization seems to be connected with a decrease in membrane permeability for sodium ions in resting conditions and with activation of electrogenic ion transport. The increase of extraneuronal potassium up to 4 mM/1 and depolarization induced by currents of 1-3 nA intensified the ethymisol effects. Ethymisol decreased efflux and influx of ions through membrane thus affecting the AP parameters. The effects of ethymisol also involved an increase of neurons excitability and intensification of synaptic activity. Neither ethyrasol nor caffein exerted these effects.

[The role of the muscarinic, adenosine and adrenoreceptors of the heart in the development of postischemic reperfusion ventricular fibrillation]. / Rol' muskarinovykh, adenozinovykh i adrenoretseptorov serdtsa v razvitii postishemicheskoi reperfuzionnoi fibrilliatsii zheludochkov.

The authors studied the effect of m-cholino-, adreno-, and purinotropic agents on the development of postischemic reperfusion fibrillation of isolated rat hearts. Pilocarpine, norepinephrine, phenylephrine, and adenosine caused a proarrhythmogenic effect. Atropine, trimedoxim, prazosin, and chloroquine made fibrillation less expressed. A direct correlation was found between the arrhythmogenic effect of reperfusion and the size of the no-reflow zone, with the use of the drugs too. It is concluded that the phospholipid mechanism contributes to realization of the arrhythmogenic effect of reperfusion and vascular disorders, leading to the occurrence of the no-reflow phenomenon.

[Action of regulators of peripheral cholinergic processes on development of early arrhythmia in myocardial ischemic rats]. / Vliianie reguliatorov perifericheskikh kholinergicheskikh protsessov na razvitie rannikh aritmii u krys pri ishemii miokarda.

Occlusion of the left coronary artery in rats provoked ventricular tachycardia (VT) and ventricular fibrillation (VF) within the first 30 min of ischemia leading to death in 20% animals. Methacin (i.v., 100 micrograms/kg) significantly prolonged VT and VF without effects on the survival. Acetylcholine (i.v., 10 micrograms/kg/min) had no influence on VT frequency and severity but prevented VF. Rats from this group survived. The same effect was observed for neostigmine (i.v., 25 micrograms/kg). Nicotine (i.v., 2.5 micrograms/kg/min) prolonged VT episode duration but did not change frequency and severity of VF and survival. Ganglioblockers hexametony and azametony (i.v., both in a dose 500 micrograms/kg) significantly attenuated VT, prevented VF and death of the animals. Thus, cholinotropic drugs may have both antiarrhythmic and proarrhythmogenic effects in early arrhythmias induced by ischemia.