Supplementary Figure 6: Chemical structure of d-CPPene and activity profile
From: Trajectory events across hippocampal place cells require previous experience
The first selective NMDAR antagonists AP5((2R)-amino-5-phosphonovaleric acid; (2R)-amino-5-phosphonopentanoate) and AP-7 had to be infused via mini-pumps directly into the brain due to poor penetration of the blood brain barrier. CPP,3-(2-Carboxypiperazin-4-yl)propyl-1-phosphonic acid, was synthesized as a rigid analog of AP-7 and is a potent, selective, and competitive antagonist of NMDA-type receptors that can be administered intra-peritoneally (Lehmann et al., 1987). D-CPPene, D-4-[(2E)-3-Phosphono-2-propenyl]-2-piperazinecarboxylic acid, is an analog of CPP, as seen above. D-CPPene is the most potent, enantiomerically pure, competitive NMDA antagonist (Lowe et al., 1990).The standard form of CPP used in previous place cell studies has been a racemic mixture including both enantiomers (D- and L-) (e.g. Ekstrom et al., 2001; Kentros et al., 1998). For both CPP and CPPene the D-enantiomer is 15-20 times more potent than the L-enantiomer. D-CPPene is 4.7 times more potent than DL-CPP and 2.2 times more potent than D-CPP (Lowe et al., 1990).
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Ekstrom, A.D., Meltzer, J., McNaughton, B.L., and Barnes, C.A. (2001). NMDA receptor antagonism blocks experience-dependent expansion of hippocampal "place fields". Neuron 31, 631-638.
Kentros, C., Hargreaves, E., Hawkins, R.D., Kandel, E.R., Shapiro, M., and Muller, R.V. (1998). Abolition of long-term stability of new hippocampal place cell maps by NMDA receptor blockade. Science 280, 2121-2126.
