Glutamate receptors allosteric modulators

These X-ray structures provide a wealth of information about the interactions of agonists, antagonists, and allosteric modulators with the glutamate receptor subunit... 

Knoflach, F., Mutel, V., Jolidon, S., et al. (2001) Positive allosteric modulators of metabotropic glutamate 1 receptor characterization, mechanism of action, and binding site. Five. Natl. Acad. Sci. USA 98,13402-13407. 

Flor, P. J., Maj, M., Dragic, Z., et al. (2002) Positive allosteric modulators of metabotropic glutamate receptor subtype 4 pharmacological and molecular characterization. Neuropharmacology 43, 286. 

Mathiesen, J. M., Svendsen, N., Brauner-Osbome, H., Thomsen, C., and Ramirez, M. T. (2003) Positive allosteric modulation of human metabotropic glutamate receptor 4 (hmGluR4) by SIB-1893 and MPEP. Br. J. Pharmacol. 138,1026-1030. 

Gasparini F, Kuhn R, Pin JP (2002) Allosteric modulators of group I metabotropic glutamate receptors novel subtype-selective ligands and therapeutic perspectives. Curr Opin Pharmacol 2 43-49... 

Just as does the GABA-benzodiazepine receptor complex discussed in Chapter 8 (see Figs. 8-18 to 8—20), the NMDA glutamate—calcium channel complex also has multiple receptors surrounding the ion channel, which act in concert as allosteric modulators (Fig. 10—24). One modulatory site is for the neurotransmitter glycine another is for polyamines, and yet another is for zinc (Fig. 10—24). The magnesium ion can block the calcium channel at yet another modulatory site, which is presumably inside the ion channel or closely related to it. Another inhibitory modulatory site,... 

We have already briefly mentioned the mechanism of action of PCP in Chapter 10 in our discussion on neuroprotective agents (Fig. 10—24). It acts as an allosteric modulator of the NMDA subtype of glutamate receptor (Figs. 13—12 and 13—13). It specifically acts to block this receptor and to decrease the flux of calcium into the cell. Phenylcyclidine itself and other agents that act at the PCP receptor may be neuroprotective, but apparently only at the expense of disrupting memory and causing psychosis (Fig. 13—13). 

Lecourtier L, Homayoun H, Tamagnan G, Moghaddam B. 2007. Positive allosteric modulation of metabotropic glutamate 5 (mGlu5) receptors reverses N-methyl-D-aspartate antagonist-induced alteration of neuronal firing in prefrontal cortex. Biol Psychiatry 62 739-746. 

Liu F, Grauer S, Kelley C, Navarra R, Graf R, et al. 2008. ADX47273 A novel metabotropic glutamate receptor 5 selective positive allosteric modulator with preclinical antipsychotic-like and pro-cognitive activities. J Pharmacol Exp Ther 327 827-839. 

Lindsley CW, Wisnoski DD, Leister WH, O Brien JA, Lemi-are W, Williams DL Jr, Burno M, Sur C, Kinney GG, Petti-bone DJ, Miller PR, Smith S, Duggan ME, Hartman GD, Conn PJ, Huff JR. Discovery of positive allosteric modulators for the metabotropic glutamate receptor subtype 5 from a series of V-(l,3-Diphenyl-lH-pyrazol-5-yl) benzamides that potentiate receptor function in vivo J. Med. Chem. 2004 47 5825. 

Renner, S. Noeske, T. Parsons, C.G. Schneider, P. Weil, T. Schneider, G. New allosteric modulators of metabotropic glutamate receptor 5 (mGluR5) found by ligand-based virtual screening. Chem. Bio. Chem. 2005, 6 (4), 620-625. 

Metabotropic glutamate receptor 5 positive allosteric modulators CPPHA (N-(4-chloro-2-[(l,3-dioxo-l,3-dihydro-2H-isoindol-2-yl)methyl]phenyl)-2-hydroxybenzamide) NCFP(N-(4-chloro-2-((4-fluoro-l,3-dioxoisoindolin-2-yl)methyl)phenyl)- picolinamide)... 

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