dizocilpine-maleate and emoxypine-succinate

It is established that the new compound, 9-[2-(4-isopropylphenoxy)ethyl]adenine (9-IPE-adenine) in a dose of 10 mg/kg per day produces neuroprotective effect in rats with brain ischemia model. 9-IPE-adenine decreased the neurologic deficiency 1.2 times more effectively (p < 0.05) than the reference drug mexidol in analogous dose, and had equal effect with this drug at 25 mg/kg per day on the neurologic deficiency and survival of animals. Electrophysiological studies in hippocampal slices in rats showed that 9-IPE-adenine depressed orthodromic population spikes in CA1 area by 42 ± 4%. Non-competitive antagonist of NMDA receptor complex MK-801, in contrast to D-AP5 (competitive NMDA receptor antagonist) and CNQX (competitive AMPA receptor antagonist), enhanced the depressive effect of the new drug more than two times. These ese results are indicative of the ability of 9-IPE-adenine to modulate the ion channel of NMDA receptor complex.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Action Potentials; Adenine; Animals; Brain Ischemia; CA1 Region, Hippocampal; Dizocilpine Maleate; Drug Administration Schedule; Excitatory Amino Acid Antagonists; Male; Neuroprotective Agents; Picolines; Rats; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate; Tissue Culture Techniques

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.

Topics: Analgesics; Animals; Antioxidants; Dizocilpine Maleate; Evoked Potentials; Excitatory Amino Acid Antagonists; Male; Picolines; Rabbits; Rats; Receptors, N-Methyl-D-Aspartate; Succinates

It has been found that mexidol (5 mM) significantly (96 +/- 2%) depressed excitatory postsynaptic current caused by step depolarization in neurons of medial vestibular nucleus of medulla oblongata slices in young (aged 13 - 17 days) male albino rats. In addition, mexidol (2,5 - 5 mM) depressed by 94 +/- 3% excitatory postsynaptic current caused by Shaffer collaterals stimulation of CA1 pyramidal neurons of hippocampal slices in young rats. Complex MK-801 (non-competitive antagonist of NMDA receptors), in contrast to CNQX (competitive AMPA receptor antagonist), considerably decreased the depressant effect of the drug in both brain structures. Therefore, the central favorable effect of mexidol can be mediated by ion mechanisms with glutamate- and GABA-ergic components, primarily by the inhibition of ion currents through NMDA receptor complex.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Animals; Antioxidants; CA1 Region, Hippocampal; Dizocilpine Maleate; Excitatory Postsynaptic Potentials; GABA Agents; Glutamic Acid; Male; Neurons; Picolines; Psychotropic Drugs; Rats; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate; Vestibular Nuclei