[Structure of glutamate receptor ion channels and mechanisms of their blockade by organic cations].
Structural determinants of blocking the glutamate receptors of AMPA and NMDA subtypes, were studied. Close location of hydrophobic and ammonium groups is necessary for affective blocking of the NMDA receptor channels, whereas blockers of the AMPA receptor channels have a distance of about 10 angstroms between these two groups. Models of the channels meeting these topographic data have been devised using a molecular mechanics approach. The accomplished studies revealed molecular basis of channel blockade of the NMDA and AMPA receptors. This may allow designing predictable new blocking compounds with a desired selectivity.
Magazanik
L G
LG
M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Acad. Sci., 194223, St. Petersburg, pr. M. Toreza, 44, Russia.
Tikhonov
D B
DB
Bol'shakov
K B
KB
Gmiro
V E
VE
Buldakova
S L
SL
Samoĭlova
M V
MV
D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000166:cytology; D002118:Calcium / Q000378:metabolism; D002412:Cations; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D057927:Hydrophobic and Hydrophilic Interactions; D066298:In Vitro Techniques; D007473:Ion Channels / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D008958:Models, Molecular; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology
D002412:Cations; D018691:Excitatory Amino Acid Antagonists; C110702:IEM 1460; C092754:IEM 1754; D007473:Ion Channels; D000644:Quaternary Ammonium Compounds; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D000218:Adamantane; D002118:Calcium
Issledovanie stroeniia ionnykh kanalov retseptorov glutamata i mekhanizmov ikh blokady organicheskimi kationami.