[Simultaneous AMPA receptor potentiation and NMDA receptor blockade as strategy for creating effective stimulants for cognitive functions].
New compounds representing derivatives of acyclic isothioureas have been synthesized, which are capable of simultaneously activating AMPA receptors and blocking NMDA receptors. In order to produce cognitive-stimulating effect, of principal importance is the pathway of NMDA receptor blockade produced by the drug. Positive influence is due to the blockade of NMDA receptors either by mechanism of rapid dissociation of intrachannel site or by inhibition of NR2B subunit of NMDA receptor. Substances that only potentiate AMPA receptor currents or only block NMDA receptors have less pronounced effect on memory than substances with ability to simultaneously potentiate AMPA receptor currents and block NMDA receptor currents. Based on these results, it is concluded that the simultaneous potentiation of AMPA receptors and blockade of NMDA receptors may be a new approach to the stimulation of cognitive functions.
Bachurin
S O
SO
Grigor'ev
V V
VV
Beznosko
B K
BK
Bolkunov
A V
AV
Kovalev
G I
GI
Proshin
A N
AN
D000818:Animals; D066298:In Vitro Techniques; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018697:Nootropic Agents / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011689:Purkinje Cells / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D018091:Receptors, AMPA / Q000819:agonists*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*
D018697:Nootropic Agents; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D013890:Thiourea