[Venotropic (phlebotropic) agents].

Data on pharmacodynamics and clinical use of venodilators, venoconstrictors and venoprotectors are discussed.

[Drug delivery to the brain with nanoparticles].

Drugs can be delivered to brain with the aid of poly(butylcyanoacrylate) (PBCA) nanoparticles coated with polysorbate 80. These carriers can penetrate BBB and deliver drugs of various structures, including peptides, hydrophilic compounds, and lipophilic compounds eliminated from brain with P-glycoprotein. When a suspension of polysorbate-coated PBCA nanoparticles is introduced into blood, apolipoproteins of the blood plasma adsorb on the particle surface and then interact with receptors of low-density lipoproteins situated in endothelial cells of cerebral vessels, thus stimulating endocytosis.

Pharmacological regulation of descending cortical control of the nociceptive processing.

Clinical and experimental data indicate that the cerebral cortex plays an important role in pain perception and endogenous antinociceptive system function. Moreover, the enhancement of descending inhibitory cortical control may be involved in the mechanisms of analgetic effect of some agents. The present study was designed to investigate the effect of cortical electrical stimulation (as a model of descending inhibitory control) on the behavioral and electrophysiological signs of nociceptive response, decipher the mechanisms involved therein and evaluate the action of central analgesics (both opioid and non-opioid) on descending cortical control.

[The descending cortical control of nociceptive signals: the neurochemical mechanisms and pharmacological control].

The purpose of the present study was to determine whether electrical cortical stimulation (as a model of descending inhibitory control) could alter the electrophysiological and behavioral signs of a nociceptive response. The inhibitory cortical influence on the neuronal activity produced by nociceptive stimuli (the tooth pulp, C-fibers of afferent somatic nerves, cardiac afferents) was most marked during electrical stimulation the somatosensory (Sn and St) and fronto-orbital cortices. In chronic experiments, somatosensory cortical stimulation delayed the development of the deafferentation pain syndrome and reduced its intensity.

[The delivery of loperamide to the brain by using polybutyl cyanoacrylate nanoparticles].

The possibility of using polysorbate 80-coated nanoparticles for the delivery of the water insoluble opioid (lyonist loperamide across the blood-brain barrier was investigated. The analgesic effect after i.v.

Significant entry of tubocurarine into the brain of rats by adsorption to polysorbate 80-coated polybutylcyanoacrylate nanoparticles: an in situ brain perfusion study.

The possibility of using polysorbate 80-coated polybutylcyanoacrylate nanoparticles to deliver low molecular polar hydrophilic drugs to the CNS has been studied. Tubocurarine (a quaternary ammonium salt) does not penetrate the normal intact blood-brain barrier. However, the injection of this drug directly into the cerebral ventricles of the brain provokes the development of epileptiform seizures as assessed by electroencephalogram (EEG).

Delivery of loperamide across the blood-brain barrier with polysorbate 80-coated polybutylcyanoacrylate nanoparticles.

Purpose: The possibility of using polysorbate 80-coated nanoparticles for the delivery of the water insoluble opioid agonist loperamide across the blood-brain barrier was investigated. The analgesic effect after i.v.

[Transport of the hexapeptide dalargin across the hemato-encephalic barrier into the brain using polymer nanoparticles].

The drug targeting to the brain by polysorbate 80-coated nanoparticles was studied. The leu-enkephalin analog dalargin was used as a model drug for investigating the drug penetration through the blood-brain barrier. The nociceptive threshold was measured by the tail flick test.

Passage of peptides through the blood-brain barrier with colloidal polymer particles (nanoparticles).

Transport of the hexapeptide dalargin across the blood-brain barrier was accomplished using a nanoparticle formulation. The formulation consisted of dalargin bound to poly(butyl cyanoacrylate) nanoparticles by sorption, coated with polysorbate 80. Intravenous injection of this formulation to mice resulted in an analgesic effect.

Opioid ligands with extraordinarily high mu-selectivity: dermorphin tetrapeptides containing thymine-modified alanine residues.

Four new [D-MetO2]dermorphin tetrapeptides with substituted N- and C-terminal groups and a thymine-modified alanine residue at position 4 were prepared and tested for their activity. All analogues were found to be mu-opioid receptor ligands. Two of them, H-Tyr-D-MetO-Phe-TalNHR (R = H, Ad) displayed an extremely high mu-opioid receptor selectivity comparable with that of the most mu-selective agonists among opioid peptides.

Stimulant effect of thyrotropin-releasing hormone and its analog, RGH 2202, on the diaphragm respiratory activity, and their antagonism with morphine: possible involvement of the N-methyl-D-aspartate receptors.

Thyrotropin-releasing hormone (TRH) was reported to stimulate respiration and abolish the respiratory depressant effect of morphine-like analgesics. Some TRH analogs which have a diminished hormonal activity may be of interest as potential non-specific opioid antagonists. The mechanism of this effect of TRH and its analogs is still unclear.

[Tumor-induced immunosuppression in breast cancer patients].

A comparative study of immunological reactivity of healthy volunteers and cancer patients with different stages of the disease was carried out. The study of 8 types of suppressor cells, chemoreceptor sensitivity and blast transformation of lymphocytes, natural killer cells, the level of immunoglobulins, regulatory subpopulation of lymphocytes, etc., has revealed several alterations in regulatory and effector links of immunity in the patients with late stages of the disease.

Antinociceptive activity of muscarinomimetic agents.

The effect of the agents with muscarinomimetic activity on the nociceptive transmission in the spinal cord was studied in spinal rats. Oxotremorine (5-20 micrograms/kg, i.v.

[The sensitivity of the blood lymphocytes in stomach cancer patients to met-enkephalin, dopamine and serotonin].

Sensitivity of blood lymphocytes to the stimulating effect of met-enkephalin and dopamine was shown to decrease at late stages of the gastric cancer (IIIB-IV) or in the case of metastases to other organs, while to the inhibitory effect of serotonin it increased as compared to early stages (I-IIA). Using specific blockers of opioid, dopamine and serotonin receptors it was shown that these effects were mediated through stimulation of respective type receptors.

[The effect of the stimulation of opioid receptors on lymphocyte functional activity in vivo].

With the aid of lymphocytes' spontaneous adhesion test and the reaction of blast transformation with phytohemagglutinin (PHA) the influence of met-enkephaline upon the functional activity of lymphocytes of healthy donors was studied in vitro. It was shown, that met-enkephaline stimulate lymphocyte spontaneous adhesion and the lymphocyte PHA-induced proliferative activity. The stimulating effects of met-enkephalin revealed in vitro were blocked by the opioid receptor blocker naloxone.

Employment of magnet-susceptible microparticles for the targeting of drugs.

It has been demonstrated in cats that magnet-susceptible microspheres and liposomes containing neuromuscular blocking agents (dipyronium, pyrocurinum and diadonium) caused a deeper inhibition of the neuromuscular transmission in the limb placed in the magnetic field than in the control limb located beyond the field. The microparticles containing a short-acting neuromuscular blocking agent diadonium appeared to have the highest selectivity of action. The present method allows a pronounced neuromuscular block in a target area to be achieved without noticeable effect on PCO2 of the exhaled air.

[Relation of the structure, rate of hydrolysis and activity of dicarboxylic acid esters].

The kinetics of enzymatic cholinesterase hydrolysis of dicarboxylic acid esters with neuromuscular blocking activity was studied in vitro. The maximum hydrolysis rate was shown to increase on elongation of the distance between ester groups both in the compounds containing a hydrophobic adamantyl radical attached to quaternary nitrogen and in bis-esters not containing adamantyl radicals. The comparison of neuromuscular blocking activity in vivo, enzymatic hydrolysis rates and activity on isolated skeletal muscle of some compounds demonstrated that in vivo activity is in a higher correlation with the maximum hydrolysis rate of the compounds that with activity in isolated skeletal muscle before or after cholinesterase inhibition.

[Effect of the stimulation of lymphocyte adrenoreceptors on antitumor immunity in vitro].

It was found that the stimulating effect of alpha-adrenomimetic mesatone in the test of lymphocyte adhesion inhibition in patients with rectum cancer in vitro was eliminated by beta-adrenergic blocker phentolamine and the inhibitory effect of beta-adrenergic antagonist propranolol. It was shown in vitro that lymphocyte chemoreceptor sensitivity to the stimulating effect of mesatone decreased and sensitivity to the inhibitory effect of isadrine increased in patients with advanced stages of rectum cancer.

[Effects of adrenoreceptor stimulation on in vitro spontaneous lymphocyte adhesion].

The influence of adrenergic agents: alpha, beta-agonists adrenalin and noradrenaline, alpha-agonist mesaton (phenylephrine) and beta-agonist isadrin on spontaneous adhesion of lymphocytes of healthy donors in vitro was studied. It was established, that the influence on lymphocyte alpha-adrenoreceptors caused stimulation, and on beta-adrenoreceptors--inhibition of the lymphocyte spontaneous adhesion. With the help of alpha-adrenoblocking agent phentolamine and beta-adrenoblocking agent propranolol it was demonstrated, that the adrenergic effects revealed were pharmacologically specific.

[Effect of dopamine on the antitumor immunity of patients with breast cancer].

The effect of dopamine in the test of lymphocyte adhesion inhibition in vitro was studied in patients with early (I-IIA) and advanced (IIIB-IV) stages of breast cancer (BC). It was shown that the stimulating effect of dopamine revealed at concentrations of 10(-7)-10(-5) M was blocked by haloperidol (10(-6) M). During a comparative study of dopamine effect at the early and advanced stages of BC it was found that sensitivity of lymphocytes to the stimulating effect of dopamine at the advanced stages of BS was significantly lower as compared to that at the early stages.