6-cyano-7-nitroquinoxaline-2-3-dione 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 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