[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.

Antiamnesic effect of combined treatment with galantamine and estradiol in middle-aged ovariectomized female rats.

The effect of chronic combined treatment with galantamine and 17beta-estradiol on passive avoidance retention was studied in middle-aged ovariectomized female rats (15 months) with scopolamine-induced amnesia. Combined treatment with galantamine and estradiol completely restored retrieval of memory traces in middle-aged ovariectomized female rats.

[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.

Combined administration of NAN-190 and 17beta-estradiol abolishes the amnesic effect of scopolamine in middle-aged ovariectomized rats.

Chronic combined administration of 5-HT1A receptor antagonist NAN-190 and 17beta-estradiol improved conditioned passive avoidance performance in middle-aged ovariectomized rats with scopolamine-induced amnesia. Our results suggest that the ovarian hormonal, cholinergic, and serotoninergic systems play a role in age-related cognitive disturbances under conditions of hypoestrogenic syndrome.

[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.

[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.

[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.

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.

[The characteristics of the cholinoreceptors on the identified TAN neuron of the giant African snail Achatina fulica]. / Osobennosti kholinoretseptorov na identifitsirovannom neirone TAN nazemnoi ulitki Achatina fulica.

Acetylcholine, nicotine, a selective agonist of N-cholinoreceptors suberildicholine dibromide, as well as a selective agonist of M-cholinoreceptors 5-methylfurmethide inhibited spike discharges in a dose-dependent manner up to a complete ceasing of the firing in cholinoreceptors situated on the identified neurone TAN of African giant snail Achatina fulica. M-cholinoblocker metamizylum completely prevented the inhibitory effect of methylfurmethide. Central cholinoblocker aetherophen completely prevented the inhibitory effect of suberildicholine dibromide. Metamizylum or aetherophen used alone were only able to decrease the inhibitory effect of acetylcholine, whereas a mixture of these agents suppressed completely the acetylcholine-induced inhibition. The findings suggest that, on the TAN membrane, nicotinic and muscarinic cholinoreceptors co-exist and function in one and the same direction.

[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.

[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.

[Results and prospects of development of neuropharmacology in the department of pharmacology of the Acad. S. V. Anichkov Research Institute of Experimental Medicine, USSR Academy of Medical Sciences]. / Itogi i perspektivy razvitiia neirofarmakologii v otdele farmakologii im. akad. AMN SSSR S. B. Anichkova NII éksperimental'noi meditsiny AMN SSSR.

Basic strategic and tactical principles of neuropharmacological studies are outlined, whose aim is to find and explore new synthetic neuro-blocking agents and substances simulating the structure of natural metabolites. The basic research has resulted in the development of new highly effective drugs and experimentally substantiated recommendations for their clinical application. The conceptions of the action mechanism of adrenergic and cholinergic agents, stimulants of tissue energy exchange, which have been formulated in the department, suggested new approaches to the pharmacological treatment of diseases of the central and peripheral nervous systems and neurogenic diseases of the gastrointestinal and cardiovascular systems.