[Topical drug administration to the inner ear. Modern state of the problem and development perspectives]. / Topicheskoe vvedenie preparatov vo vnutrennee ukho. Sovremennoe sostoianie problemy i perspektivy razvitiia.

The work assessed modern methods of drug delivery through biological barriers to the lesion, in particular, through the most studied - skin. The main advantages and disadvantages of the existing methods for the topical administration of drugs into the inner ear - intra-imperial and intra-labyrinth delivery are analyzed. A brief review of medicinal substances for topical administration to the inner ear, both widely used (for example, aminoglycosides, steroid drugs) and undergoing clinical trials, is given. An assessment is made of the prospects for the use of transmembrane drug delivery to the inner ear using an electric field, which has a combined electro-creative and iontophoretic effect.

[Effect of damage integrity rat brain synaptic membranes on the functional activity GABA(A)-receptor/Cl(-)-ionophore complex in the CNC].

Functional activity of the CGABA(A)-receptor/Cl(-) ionophore complex was investigated the muscimol-stimulated entry of the radioactive isotope 36Cl(-) in synaptoneurosomes in changing the structure and permeability of neuronal membranes. Integrity of the membranes was damaged by removal of Ca(+2) and Mg(+2) from the incubation medium and by the method of freezing-thawing synaptoneurosomes. In both cases, an increase in basal 36Cl(-) entry into synaptoneurosomes, indicating increased nonspecific permeability of neuronal membranes, and decreased activity the CABA(A)-receptor/Cl(-) ionophore complex. The conclusion about the relationship of processes damage neuronal membranes and reducing the inhibitory processes in the epileptic focus.

Cl- conduction of GABA(A)-receptor complex of synaptic membranes of rat brain cortex after development of chronic epileptization of the brain (pharmacological kindling).

Experiments on Wistar rats showed that basal and muscimol-induced 36Cl- entry into synaptoneurosomes isolated from the brain cortex decreased after kindling (30 mg/kg pentylenetetrazole intraperitoneally for 30 days) in animals with seizure severity score 4-5. Changes in Cl- conduction during kindling are discussed.

Effect of classic convulsants on Cl- conductance of the GABA(A) receptor complex in membranes of cerebral cortex cells at the early stage of kindling.

Muscimol-stimulated Cl- conductance of synaptoneurosomes from the cerebral cortex of Wistar rats increased during the early stage of pharmacological kindling not inducing the seizure response in animals. Picrotoxin, bicuculline, and pentylenetetrazole potentiated inhibition of muscimol-dependent 36Cl- entry into synaptoneurosomes, which attested to increased sensitivity of the GABA(A) receptor/Cl- ionophore complex to classic convulsants.

Cl(-) conduction of GABAA receptor complex of synaptic membranes in the cortex of rats at the middle stage of chronic cerebral epileptization (pharmacological kindling).

Experiments on Wistar rats showed a decrease in basal and muscimol-stimulated 36Cl(-) entry into synaptoneurosomes isolated from the cerebral cortex during the middle stage of kindling (30 mg/kg pentylenetetrazole intraperitoneally for 14 days) characterized by the development of convulsions of higher (2 points) severity in comparison with the previous stage.

Cl- conduction of GABA(A) receptor complex on synaptic membranes in rat cortex at the early stage of chronic cerebral epileptization.

Experiments on Wistar rats showed that muscimol-stimulated Cl(-) conduction of synaptoneurosomes, isolated from the cerebral cortex increased after 5-day systemic treatment with subconvulsive doses of pentylene tetrasole during the initial stage of pharmacological pentylene tetrasole kindling, characterized by gradually augmenting convulsive readiness of the brain. This indicates an increase in functional activity of the GABA(A) receptor/Cl(-) ionophore complex.

Effect of single injection of pentylenetetrazole in a subconvulsive dose on Cl- conductance of the GABAA-receptor complex.

Muscimol-stimulated Cl(-)conductance in brain cortex synaptoneurosomes from Wistar rats decreased 15 min after single intraperitoneal injection of pentylenetetrazole in a subconvulsive dose. These changes reflected a decrease in functional activity of the GABA(A)-receptor/Cl(-)ionophore complex. Muscimol-stimulated Cl(-)conductance in synaptoneurosomes returned to normal 48 h after pentylenetetrazole administration.

[Effects of corazol on the regulation of GABAa receptor-channel complex]. / Deistvie korazola na reguliatsiiu GAMKa-kanal-retseptornogo kompleksa.

Effects of corazol (pentylenetetrazole, PTZ) on the GABAA receptor-channel complex mediated 36Cl- influx into synaptoneurosomes isolated from rat cerebral cortex, were studied. PTZ inhibited the 36Cl- influx stimulated by a GABA agonist, muscimol, concentration-dependently with an IC50 of 2.11 +/- 0.25 mM. In addition, the rate of muscimol-dependent desensitization of the GABAA receptor-channel complex was significantly reduced in the presence of PTZ. Apparently, the superimposition of these two mutually opposing effects is the cause of a mixed (competitive/noncompetitive) type of inhibition displayed by PTZ. The rate of desensitization of GABAA receptor-channel complex is suggested to be regulated by intracellular concentration of Cl- through a feed-back mechanism.

Effect of ethanol and DSIP on the 36Cl-flux in synaptosomal vesicles.

Delta-sleep-inducing peptide (DSIP) is an endogenous substance that regulates the response of the organism to stress. It was found that DSIP, like diazepam and ethanol, activates muscimol-stimulated 36Cl- uptake in the rat brain cortex and partially counteracts the stimulatory action of ethanol on this process. The effect of peptide disappears at the lowering of the incubation temperature. We propose that DSIP is a concordant regulator partly mediating its action through the membrane phospholipids.

[Increase in glutamate decarboxylase activity in the synaptosomes after treatment with tetanus toxin]. / Uvelichenie aktivnosti glutamatdekarboksilazy v sinaptosomakh pri deistvii stolbniachnogo toksina.

The tetanus toxin (TT) action on crude glutamic acid decarboxylase (GAD) preparation and GAD activity of synaptosomes were studied. TT was not found to affect GAD, but the GAD activity of synaptosomes isolated from the rat brain cortex increased by 46% after 15 min of incubation in the presence of a dose of 0.1 DLM TT. In some experiments, the GAD activity of a crude synaptosomal fraction isolated from TT affected lumbar segments of the rat spinal cord 48 hours after 0.2 DLM TT injection into the m. gastrocnemius was higher than in the control. If the GAD activity was evaluated in the presence of saturating concentrations of pyridoxal-5-phosphate, the difference in the GAD activities between the control and TT-affected synaptosomes (in vivo and in vitro) was not revealed. These findings allow the suggestion that the TT influences on GABA synthesis are mediated by membrane processes and that they occur at the level of the cofactor and apoenzyme interaction.

[Effect of tetanus toxin on K+ and Na+ concentration in synaptosomes]. / Vliianie stolbniachnogo toksina na soderzhanie K+ i Na+ v sinaptosomakh.

A study was made of the effect of tetanus toxin (TT) in doses of 20-1000 MLD (for rats) on synaptosomes isolated from the rat brain cortex. TT produced a decrease in K+ content in synaptosomes. The effect depended on the dose of TT (I50=22 MLD). The content of Na+ remained unchanged. The action of TT depended on the time and the maximal effect was seen upon 60 minutes of incubation. TT inactivated by boiling or by antitoxin did not affect K+ content in synaptosomes. An increase of K+ concentration up to 17 mM in an incubation medium led to an increase in K+ content in TT-poisoned synaptosomes but not in the control ones. Possible changes in membrane electrogenesis in nerve terminals caused by TT are discussed.