[Experimental study of the effectiveness of local anesthetic activity of a new dimethylphenylacetamide-containing pharmaceutical composition in chronic periodontitis]. / Eksperimental'noe issledovanie po otsenke effektivnosti mestnoanesteziruyushchei aktivnosti novoi dimetilfenilatsetamid-soderzhashchei farmatsevticheskoi kompozitsii pri khronicheskom periodontite.

Novel anaesthetic formulation LHT-15-32 was studied. The experimental study involved 66 white mice, 15 Rana radibunda frogs and 50 male Sprague Dawley rats. Its acute intravenous and subcutaneous toxicity was determined in mice. Pain sensitivity threshold of upper second molar was determined in rats with experimental periodontitis. Oxidative stress activity and total antioxidant capacity were determined in rats' gingival mucosa by induced chemiluminescence. Tissue IL-1ß, IL-10 and TNF-a concentration was quantitatively assessed by ELISA. LHT-15-32 Na-blocking activity was studied on isolated neurons of Limnea stagnalis para-pharyngeal ganglion. Rana radibunda isolated sciatic nerve was perfused with LHT-15-32 to assess its conductivity. LHT-15-32 acute intravenous and subcutaneous toxicity was lower then that of its active substance LHT-4-00. The formulation infraorbital administration induced deep dental anaesthesia lasted longer than 70 min, activated local antioxidant defence system and decreased IL-1ß level in gingival tissue. At 10-6 to 10-3 M LHT-15-32 inhibited sciatic nerve conductivity and blocked Na+-channels of isolated neurons in dose-dependent manner. LHT-15-32 proved to be less toxic than active substance and lidocaine. The agent provides deep and prolonged anesthesia of the upper molar of rats in chronic apical periodontitis, lowers tissue concentration of pain cascade cytokines and oxidative stress activity and suppresses the action potential amplitude of a sensory nerve due to Na-blocking activity.

Neuroprotective and Antiamnestic Effects of a New Drug Emopag in Rats.

Emopag, a new drug, preventively administered in doses of 10 and 30 mg/kg/day over 4 days produced a pronounced neuroprotective effect in the model of brain ischemia caused by gravitational overload and reduced animal mortality from 17 to 0%. The preparation more effectively corrected neurological deficit than the reference drugs Mexidol (in considerably larger doses of 30 and 90 mg/kg/day) and antihypoxic drug amtizol (30 mg/kg/day). Moreover, Emopag exhibited considerable antiamnestic activity comparable to that of Mexidol (in 3-fold higher doses); in a dose of 30 mg/kg/day Emopag was more effective than Mexidol and amtizol in the same dose. Thus, Emopag showed marked neuroprotective and antiamnestic effects in the model of gravitational overload in rats.

Aminoethane Sulfonic Acid Magnesium Salt Inhibits Ca2+ Entry Through NMDA Receptor Ion Channel In Vitro.

The effect of a cerebroprotective agent magnesium bis-aminoethanesulfonate (laboratory code FS-LKhT-317) on intracellular calcium concentration was studied by the fluorescent imaging technique on neuroglial cell culture from Spraque-Dawley rat hippocampus. The substance produced a pronounced inhibitory effect and suppressed NMDA receptor activity in concentrations of ≥50 µM. The observed effects were reversible or partially reversible and were detected by a decrease in Ca2+ signal amplitude in neurons in response to NMDA applications in a Mg2+-free medium and by inhibition of Ca2+ pulses in magnesium-free medium (elimination of magnesium block).

[STUDYING SOME PHARMACOLOGICAL EFFECTS OF NEW 3-HYDROXYPYRIDINE DERIVATIVE].

It was established that a new 3-hydroxypyridine (3-HP) derivative, 2-ethyl-6-methyl-3-hydroxypyridine L-aspartate (3-HP), in small doses (1 and 5 mg/kg) increased physical performance in treadmill and swimming tests on rats. The new substance showed greater or equal effects compared to the reference actoprotector drugs metaprot and ladasten in much higher doses. The gluconeogenesis inhibitor tryptophan significantly (74 ± 5%, p < 0.01) prevented this stimulatory effect of 3-HPA in the treadmill test on rats. 3-HPA at a higher dose (30 mg/kg) had marked antiamnesic effect on various models of amnesia in mice. It was more effective than reference drugs mexidol (another 3-HP derivative) in a dose of 30 mg/kg and nootropic drug piracetam in a dose of 200 mg/kg, but had equal effect with these drugs in doses of 50 and 800 mg/kg, respectively. 3-HPA (30 mg/kg per day) had neuroprotective effect in rats with brain ischemia and decreased the neurologic deficiency more effectively than mexidol (50 mg/kg per day).

[VESTIBULAR AND THERMOPROTECTIVE PROPERTIES OF A NEW ACTOPROTECTOR].

In experiments with rats, a new 3-hydroxypyridine (3-HP) derivative--2-ethyl-6-methyl-3-hydroxypyridine L-asparaginate (30 mg/kg)--exhibited a strong vestibuloprotective effect which was better than of promethazine (50 mg/kg), a well-known vestibuloprotector Besides the new actoprotector was competitive with another 3-HP derivative, namely, mexidol (ethyl-methyl-hydroxypyridine succinate) (100 mg/kg). Moreover, a distinct thermoprotective effect of 2-ethyl-6-methyl-3-hydroxypyridine L-asparaginate (30 mg/kg) in mice was not worse than that of mexidol or metaprot (ethylthiobenzimidasol, former name bimethy), an actoprotector with good thermoprotective properties. To conclude, owing to the membrane-protective and antioxidative qualities, the vestibuloprotective and thermoprotective properties of 2-ethyl-6-methyl-3-hydroxypyridine L-asparaginate are better or competitive with the reference preparations.