[The safety of selective serotonin reuptake inhibitors: hemostasis].

The literature data of the reaction of haemostatic system to antidepressants from the group of selective inhibitors of serotonin reuptake are summarized. The development of haemorrhagic complications is analyzed. The risk/benefit ratio is estimated for the treatment of depression in patients with acute myocardial infarction and stroke. A differential approach to indication of antidepressants is substantiated for the treatment of comorbid depressive disorders in different types of somatic pathology.

[GABA-system and alcohol: does an "ethanol receptor" exist? (review)].

There are two alternative points of view in the current literature addressing the mechanisms of ethyl alcohol effects on cells. A historically first appeared hypothesis of ethanol influence on living systems is based on the physical-chemical background and described the membrane-associated and intracellular biochemical events as a consequence of changes in the membrane state. In opposite, the attempts exist to differentiate the "specific action" of alcohol on separate neurochemical systems. The pharmacological belonging of ethanol to the class of CNS sedative drugs is explained in a mechanistic way through its "specific" action at GABA- and glycine-ergic systems. In the present article, the author analyses the basic results of the latter hypothesis and concludes that evidence of the existence of so-called "ethanol receptor" is insufficient.

[An integral chip for the multiphase pulse-duration modulation used for voltage changer in biomedical microprocessor systems]. / Integral'naia mikroskhema upravleniia mnogofazovoi shirotno-impul'snoi moduliatsiei dlia preobrazovatelia napriazheniia v biomeditsinskikh mikroprotsessornykh sistemakh.

An integral chip (IC) was designed for controlling the step-down pulse voltage converter, which is based on the multiphase pulse-duration modulation, for use in biomedical microprocessor systems. The CMOS technology was an optimal basis for the IC designing. An additional feedback circuit diminishes the output voltage dispersion at dynamically changing loads.

[The endogenous allosteric regulators of receptors]. / Endogennye allostericheskie reguliatory retseptorov.

The literature data devoted to endogenous allosteric regulators of membrane bound receptors are summarized in the present review. The allosteric processes are classified to (i) cooperative interaction, (ii) nonspecific, (iii) functional, and (iv) specific regulations according to target topography in a receptor. The specific endogenous allosteric regulators are described for GABAA, NMDA, muscarinic, nicotinic, serotonin, and opioid receptors. Substances of different chemical structure (peptides, lipids, and polycyclics) are able both to activate or inhibit binding and function of respective receptors. Some pathological processes appear to depend on endogenous receptor modulators. The role of the regulators is speculated in terms of receptor homeostasis, in particular, counteraction of receptor tolerance and/or sensitisation during physiological pulsation in a ligand' level in synaptic cleft.

[Allosteric regulation of receptors. I. Cooperative interaction and functional regulation]. / Allostericheskaia reguliatsiia retseptornykh sistem. I. Kooperativnoe vzaimodeistvie i funktsional'naia reguliatsiia.

Today thousands of scientific publications in the field of receptology are dedicated to allosteric regulation of receptors. Biochemical events in cardiovascular, nerve, immune, endocrine, and other systems are based on various allosteric processes. Many of pharmaceuticals exert their action via allosteric regulation of receptive structures. Unfortunately, original publications sometimes are rather fragmentary. The history, methodology, classification as well as functional aspects of allosteric regulation of receptors are reviewed in the present paper. On the basis of topography of orthosteric and allosteric receptor binding sites allosteric regulation may be subdivided into: specific, non-specific, functional, and cooperative interaction. The results of allosteric regulation of receptors by metal cations are summarized. Agonists and antagonists receptor interaction are described from the point of view of allosteric regulation.

[Regulation of opioid receptors by thyroliberin analogues]. / Reguliatsiia opiodnykh retseptorov analogami tiroliberina.

The ability of thyroliberin (TRH) to interact with opioid receptors (OR) was studied using radioligand analysis. TRH did not influence specific binding of [3H]-naloxone, but increased affinity of high affinity binding sites for the ligand in a dose-dependent manner. TRH also decreased affinity of low- affinity binding sites. Kinetic analysis of low-affinity binding sites suggests the existence of at least two subpopulations of OR, which differed in their affinity to naloxone and mode of interaction with TRH. TRH acted as non-competitive and competitive inhibitor of receptor binding sites with the lowest and moderate affinity, respectively. The allosteric pattern of TRH influence on OR with high and the lowest affinity to naloxone was suggested. TRH analogues were estimated for their ability to change in OR binding characteristics. The level of [3H]-DADL specific binding was not influenced by the peptides tested but the affinity was changed. Blind control experiment showed the ability of the TRH relative substances to increase in affinity of d-receptors could be ranked in the row: dihydroorotyl-hystidyl-prolinamide > TRH > methionyl-asparagyl-phenylalaninamide. This is consistent with ability of these compounds to influence the dopaminergic events.

[The effect of reaferon on the opioid systems of chronically alcoholized rats]. / Vliianie reaferon na opioidnye sistemy khronicheski alkogolizirovannykh krys.

Chronic alcoholic intoxication is followed by a fall in 3H-(D-ala-2,D-leu-5)-enkephalin affinity of mu-opioid receptors with their unchanged concentrations in the rat brain cortex, by reductions in the tissue and plasma levels of beta-endorphine and met-enkephalin. A daily administration of reaferon in a dose of 10,000 IU during two fortnights completely restored both the binding affinity of the receptors and the concentrations of the peptides tested: those of beta-endorphine in the adenohypophysis and plasma and those of metenkephalin in the adrenals and plasma.

[Opiate reception in the rat brain: the effect of chronic consumption of alcohol and reaferon]. / Opiatnaia retseptsiia v golovnom mozgu krys: Vliianie khronicheskogo potrebleniia alkogolia i reaferona.

Binding properties of opiate receptors were studied in brain tissue of alcoholized rats after administration of the interferon-derived drug reaferon using equilibrium radioreceptor assay. Chronic alcohol intoxication was accompanied by a decrease in affinity of opiate mu-receptors for ligands in the animals with alcohol intoxication and ethanol withdrawal. Alterations in parameters of delta-reception and in content of mu-receptors were not found. Daily administration of reaferon at a dose of 10(4) U within 1.5 month did not affect these impairments, observed in rats, studied in intoxication. However, the drug reduced completely the alcohol effect on receptors during the withdrawal period. Possible normalizing effects of reaferon on the state of opiate receptors are discussed.

[Blood levels of opioid peptides and alpha interferon under the action of dipyridamole]. / Soderzhanie opioidnykh peptidov i al'fa-interferona v krovi pri deistvii dipiridamola.

The levels of met-enkephalin (ME), beta-endorphin (BE), and alpha-interferon (a-IFN) have been determined in the human blood 1 day after dipyridamole administration. Dipyridamole led to an increase in serum a-IFN concentration up to 3 times, and to simultaneous rise of the lymphocytes ability to produce a-IFN. The content of BE did not depend on dipyridamole treatment, but ME level achieved 110 +/- 4.8 pg/ml (compare to 79.5 +/- 7.6 pg/ml in control). Positive interrelation has been found out between individual ME concentrations and lymphocyte abilities to a-IFN production with the coefficient of correlation equal to 0.69. The effect of dipyridamole on ME level is suggested to develop via a-IFN interaction with the opioid systems.

[Modification by alpha-interferon of ethanol-induced changes in the level of opioid peptides in the rat striatum and hypophysis]. / Modifikatsiia pod vliianiem alpha-interferona vyzvannykh étanolom izmenenii soderzhaniia opioidnykh peptidov v striatume i gipofize krys.

Content of Met-enkephalin in striatum and of beta-endorphin in rat hypophysis were estimated after administration of ethanol and alpha-interferon into the animals. Ethanol decreased Met-enkephalin content in striatum and of beta-endorphin in hypophysis. Preadministration of alpha-interferon into brain ventricles before ethanol administration led to an increase in concentration of Met-enkephalin, while content of beta-endorphin was unaltered. In peripheric administration alpha-interferon normalized content of beta-endorphin in adenohypophysis but did not affect the Met-enkephalin concentration. Effects of alpha-interferon on content of Met-enkephalin and beta-endorphin, related to dissimilar organization of the opiate systems in hypophysis and striatum tissues, are discussed.

[Specific binding of mu- and delta-ligands by opiate receptors in the rat brain in the presence of reaferon]. / Spetsificheskoe sviazyvanie mu- i delta-ligandov opiatnymi retseptorami golovnogo mozga krys v prisutstvii reaferona.

The ability of recombinant alpha 2-interferon (reaferon) to compete for opiate binding sites with mu- and delta-selective compounds was determined. Reaferon was found to inhibit the binding of 3H-D-ala2, D-leu5-enkephalin, and Ki value calculated was equal to 8.5 +/- 2.6 U.10(-3)/ml. The mu-agonists reception levels were decreased in the presence of reaferon at concentrations above 500 U/ml; the Ki values for 3H-morphine, 3H-dihydromorphine, 3H-RX 783006 were found to be 3.25 +/- 0.35, 4.28 +/- 0.81 and 6.51 +/- 1.27 U.10(-4)/ml, respectively. When reaferon was added into reaction medium at concentrations more than 5.10(3) U/ml the specific receptor binding of opiate antagonist 3H-naloxone was demonstrated to be increased and this effect was reversed with 100 mM NaCl. The existence of allosteric reaferon binding site which coupled with naloxone sensitive receptor was suggested to explain the results obtained.

[Opiate receptor binding of naloxone in the rat brain: effect of sodium ions]. / Opiatnaia retseptsiia naloksona v golovnom mozge krys: vliianie ionov natriia.

The binding levels and opiate receptor binding parameters were determined for 3H-naloxone in rat brain in the presence of NaCl added in vitro. An addition of NaCl at concentrations of 5-35 mM to the reaction medium caused an increase in the level of the antagonist receptor binding. The maximal level of 3H-naloxone reception activation was observed in the presence of 10-20 mM NaCl and was, on the average, 25%. Both the increase in the NaCl dose in vitro and its decrease caused a gradual diminution of the Na+ effect. An analysis of opiate receptor saturation with 3H-naloxone revealed that the label interacted with one type of the binding sites irrespective of NaCl concentration. The affinity of receptor binding sites for 3H-naloxone increased already at NaCl concentration of 2.5 mM. In contrast, the apparent maximal number of binding sites did not change after NaCl addition at concentrations which coincided with the intracellular Na+ level but was decreased with an increase (up to 50-100 mM) in NaCl present in the reaction mixture. The results obtained point to the existence of two different binding sites that are coupled with the 3H-naloxone reactive opiate receptor.

[Alpha interferon interaction with opiate receptors in the rat brain]. / Vzaimodeistvie al'fa-interferona s opiatnymi retseptorami golovnogo mozga krys.

The preferential interactions of alpha-interferon (alpha-IFN) with delta and mu opiate receptors were studied. alpha-IFN (specific antiviral activity 2 X 10(3) U/mg protein) was shown to inhibit in the competitive manner 3H-naloxone and 3H-D-ala2, D-leu5-enkephalin (3H-DADL) specific binding to opiate receptor subpopulations. alpha-IFN was much more effective in decreasing 3H-DADL than 3H-naloxone binding in opiate receptors: K1 values averaged 160 +/- 30 and 1150 +/- 80 U/ml, respectively. IFN effective concentrations inhibiting 50% of 3H-naloxone opiate receptor binding in the absence or presence of 100 mmol/l NaCl were similar, and the "sodium shift" value was equal to 1. The independence of alpha-IFN activity of the presence of NA+ cations suggests the antagonist character of alpha-IFN interaction with opiate receptors. Thus, alpha-IFN employed appears to be an alpha-selective ligand displaying the in vitro properties of "pure" morphine antagonists.

[Effect ot thyroliberin on rat brain opiate receptors]. / Vliianie tiroliberina na opiatnye retseptory golovnogo mozga krys.

The ability of thyroliberin to interact with opiate receptors of the rat midbrain and hypothalamus has been studied. It was shown by competitive displacement analysis that thyroliberin did not replace labeled opioid peptides in opiate receptor binding sites when added in vitro at concentrations of up to 10(-5) M. The specific binding of opioid peptides was increased by 10-20% in the presence of 10(-7)-10(-6) M thyroliberin. This effect was, probably, due to the rise in the affinity of high-affinity opiate receptors. At the same time the affinity of low-affinity binding sites was decreased. It is suggested that the antagonistic properties of thyroliberin are mediated by the modulation of the binding characteristics of enkephalin-low-affinity opiate receptors.

[Interaction of various tetrahydroisoquinoline alkaloids with opiate receptors in the rat hypothalamus and midbrain]. / Vzaimodeistvie nekotorykh tetragidroizokhinolinovykh alkaloidov s opiatnymi retseptorami gipotalamusa i srednego mozga krys.

Using the method of competitive displacement of 3H-labelled naloxone, (D-ala2)-met enkephalinamide or (D-ala2)-D-leu-enkephalin by salsolinol, 1-methyl-6-hydroxy-1, 2, 3, 4-tetrahydro-beta-carboline or 1-methyl-6-methoxy-1, 2, 3, 4-tetrahydro-beta-carboline from opiate receptors, it was shown that the alkaloids studied were capable to cause specific interactions with rat hypothalamus and midbrain however, exhibiting distinctly less affinity as compared with morphine or its analogs. The sodium ratios, determined from the effective doses of the tetrahydroisoquinoline alkaloids corresponding to the alkaloid concentrations, which induce 50% displacement of 3H-naloxone from the opiate receptors in the presence or absence of 100 mM NaCl, have been found to be 0.75 for salsolinol and 3.6 for beta-carbolines studied. The data obtained suggest that salsolinol, similar to naloxone, is a "pure" morphine antagonist, whereas the beta-carbolines studied may be classified with the agonist-antagonist type. A considerable decrease in the affinity of mu-type opiate receptors has been found in presence of salsolinol in the incubation medium. The possible mechanisms of pharmacological action of the alkaloids and their relation to development of alcohol dependence and tolerance are discussed.