Another Baudry paper, this one combining CX-546 and an ACHase inhibitor, and various other combinations. BTW, Cortex has a use patent covering AMPA upmodulators when used in combination with ACHase inhibitors. Baudry's company Lifelike Biomatic appears to be trying to circumvent some of Cortex's broad patents by various approaches - 1) by using sub-therapeutic doses of AMPA modulators combined with NMDA modulators ("Nemdakines") to achieve a synergistic effect, as well as 2) structurally fusing an AMPA upregulator moiety with an NMDA modulator moiety into a single molecule. Clever ideas, if they work -
>>> Program#/Poster#: 39.10/D22
Title: Positive modulators of AMPA but not NMDA receptors potentiate the effects of cholinesterase inhibitors on LTP
Location: Georgia World Congress Center: Halls B3-B5
Presentation Start/End Time: Saturday, Oct 14, 2006, 2:00 PM - 3:00 PM
Authors: *M. M. CHOU, X. XIE, T. W. BERGER, M. BAUDRY;
Neuroscience Program, Univ So California, Los Angeles, CA.
LTP induction requires activation of both AMPA and NMDA receptors and positive modulators of both classes of receptors have been shown to facilitate LTP induction. Acetylcholinesterase inhibitors (AChEI) increase cell excitability and there is substantial evidence that they improve learning and memory although their effects on LTP induction have not been studied extensively. In the present study, we tested potential synergistic interactions between positive modulators of AMPA receptors or NMDA receptors and AChEIs on LTP induction in field CA1 of acute hippocampal slices from young male rats. The positive AMPA receptor modulators, CX-546 and piracetam, and the positive NMDA modulator, D-serine, were used at concentrations that were ineffective to facilitate LTP induction. Similarly, several AChEIs, rivastigmine, donepezil and galantamine, were used at concentrations that produced no or minimum effects on LTP induction. The combination of CX-546 or piracetam but not of D-serine with any of the AChEIs resulted in marked enhancement of LTP. This effect was completely blocked by atropine, a muscarinic receptor blocker. The analysis of the effects of the compounds alone and of the various combinations of modulators and AChEIs on short-term potentiation (STP), LTP and burst responses indicated that, despite the fact that the inhibitors act on the same target, they each produce a distinct pattern of effects. The marked synergy observed on LTP induction suggests that some of these combinations might provide new avenues for the treatment of patients with cognitive impairment. <<<
