[Combined blockade of GluR1 AMPA and NMDA receptors effectively eliminates neurological disorders in rats with experimental allergic encephalomyelitis].
The experimental allergic encephalomyelitis (EAE) developed on the 11 - 12th day after inoculation of encephalitogenic mixture in 96% of female Wistar rats in the control group. In the majority of control rats, severe EAE with a long duration of action prevailed (average cumulative index, 25.6; average duration of illness, 15.8 days). A course of NMDA-antagonist memantine administration in a doze of 10 and 20 mg/kg prevented the development of EAE in 10% of rats. In rats with EAE (on the average, 12-13 days after the administration of encephalitogenic mixture) the drug slightly reduced the severity and duration of neurological disorder: the average cumulative index and duration of illness decreased by a factor of 1.4-1.5 in comparison to the control. The antagonist of NMDA and GluR1 AMPA receptors, IEM-1913, upon a course of administration in a doze of 0.1-1 mg/kg prevented the EAE development in 23-25% of rats. In the rats with EAE treated with IEM-1913 in the maximum doze (1 mg/kg), the EAE developed only after completion of the course of drug administration (on the 19-20th day), proceeded quickly (no more than 5 days), and in the easy form (average cumulative index. 8.3). High efficacy of IEM-1913 administration in rats with EAE is apparently connected with its neuroprotective and antiinflammatory action, which is related, on the one hand, to a combined block of NMDA and GluR1 AMPA of receptors in brain and, on the other hand, to a reduction of the permeability of BBB for encephalitogenic T-lymphocytes owing to the blockade of NMDA receptors in BBB.
Abdarasulova
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Serdiuk
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Gmiro
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D000818:Animals; D001952:Bridged-Ring Compounds / Q000627:therapeutic use*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000517:prevention & control*; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005260:Female; D008559:Memantine / Q000627:therapeutic use*; D011700:Putrescine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D001952:Bridged-Ring Compounds; D018691:Excitatory Amino Acid Antagonists; D008559:Memantine; D011700:Putrescine; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C526128:IEM 1913