[Analgesic effect of succinate-containing preparations].

It was established that mexidol (100 mg/kg, i.v.) in contrast to cytoflavin (1 ml/kg, i.v.) and reamberin (100 mg/kg, i.v.) produced analgesic effect in rabbits by raising pain threshold under electric stimulation of dental pulp. Mexidol (200 mg/kg, i.p.) also raised the nociceptive threshold of the same tail stimulation by in rats (vocalization test). Non-competitive antagonist of NMDA receptor complex, MK-801 (0.1 mg/kg, i.p.), and selective GABAA receptor antagonist bicuculline (1.5 mg/kg, i.p.) decrease the effect of mexidol. Therefore, the antinociceptive effect of mexidol in rats is mediated by the NMDA receptor complex and GABAA receptors. It was also found that mexidol (microiontophoretic application) produced inhibiting effect on spontaneous and evoked (caused by nociceptive electric stimulation of hind paw) activity of neurons (major part) of sensorimotor cortex and ventral posterior thalamic nucleus in rabbits. On the background of MK-801 and GABA blockers (bicuculline and picrotoxin), this action of mexidol was completely prevented or considerably decreased (by almost 80 and 60% of cells, respectively). Therefore, the effect of mexidol on these neurons is realized by inhibiting ion currents through NMDA receptor complex and via GABAA/benzodiazepine receptor complex.

[Comparative study of the influence of succinate-containing preparations on mitochondrial respiration in rat brain cells].

It has been established by polarographic measurements that preparations containing succinate, such as cytoflavin (0.85 mM succinate), mexidol, and amtizol succinate (at a concentration of 0.85 mM) but not reamberin (0.045 mM succinate), nearly equally (by 35-45%) increase oxygen consumption in rat brain mitochondria. On the other hand, malonate - inhibitor of the respiratory complex II (succinate dehydrogenase) of mitochondrial chain suppressed the stimulating effect of these drugs.

[Comparative studies of antihypoxic, neuroprotective and analgesic action of succinate-containing drugs].

Experiments with mice showed that, unlike reamberin (100 mg/kg), mexidol (100 mg/kg) and cytoflavin (1 ml/kg) act as antihypoxants in pressure and hermetic chambers but not in case of acute hemic and histotoxic hypoxia. Amtisol succinate (100 mg/kg), a reference antihypoxant, excels the other tried succinate-containing drugs in all models of acute hypoxia except the hermetic chamber. In addition, the neuroprotective action of mexidol (100 mg/kg/d) and cytoflavin (100 ml/kg/d) in rats with induced ischemic stroke which was stronger than that of reamberin and amtisol succinate (100 mg/kg/d). Besides, mexidol (100 mg/kg) but not cytoflavin (1 ml/kg), reamberin or amtisol succinate (100 mg/kg) had a distinct analgesic effect in rabbits. On the neuronal level, mexidol interacts with the GABAA- benzodiazepine-receptor complex in nearly 60% cells and inhibits ion currents through the NMDA-receptor ion channels in nearly 80% neurons.