Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Jan 23;10(3):228-236.
doi: 10.1021/acsmedchemlett.8b00450. eCollection 2019 Mar 14.

Allosteric Modulation of Ionotropic Glutamate Receptors: An Outlook on New Therapeutic Approaches To Treat Central Nervous System Disorders

Simone Brogi  1   2 , Giuseppe Campiani  1 , Margherita Brindisi  1 , Stefania Butini  1
Affiliations

Allosteric Modulation of Ionotropic Glutamate Receptors: An Outlook on New Therapeutic Approaches To Treat Central Nervous System Disorders

Simone Brogi et al. ACS Med Chem Lett. .

Abstract

The allosteric targeting of ionotropic glutamate receptors (iGluRs) is a valuable approach for treating various central nervous system (CNS) disorders. In this frame, this Innovations provides a summary of the state-of-the art in the development of allosteric modulators for iGluRs and offers an outlook regarding innovative strategies for treating neurological diseases.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Chemical structures of DETQ (PAM selective for dopamine receptor-1), SB269652 (NAM selective for dopamine receptors-2/3), and representative approved allosteric modulators.
Figure 2
Figure 2
Structural view of AMPA (A) and NMDA (B) receptors highlighting known allosteric binding sites for PAMs and NAMs. (Pictures were generated by PyMOL using the PDBs 5WEO (AMPAR) and 4PE5 (NMDAR) and the information in ref (9).)
Figure 3
Figure 3
Chemical structures of γ-8 TARP-dependent-AMPARs antagonists (LY3130481/CERC-611, JNJ-55511118, and JNJ-56022486) and γ-2 TARP AMPARs modulators (VU0612951, VU0627849, and VU0539491).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Changeux J. P.; Christopoulos A. Allosteric Modulation as a Unifying Mechanism for Receptor Function and Regulation. Cell 2016, 166, 1084–1102. 10.1016/j.cell.2016.08.015. - DOI - PubMed
    1. Johnstone S.; Albert J. S. Pharmacological property optimization for allosteric ligands: A medicinal chemistry perspective. Bioorg. Med. Chem. Lett. 2017, 27, 2239–2258. 10.1016/j.bmcl.2017.03.084. - DOI - PubMed
    1. Nussinov R.; Tsai C. J.; Csermely P. Allo-network drugs: harnessing allostery in cellular networks. Trends Pharmacol. Sci. 2011, 32, 686–693. 10.1016/j.tips.2011.08.004. - DOI - PMC - PubMed
    1. Foster D. J.; Conn P. J. Allosteric Modulation of GPCRs: New Insights and Potential Utility for Treatment of Schizophrenia and Other CNS Disorders. Neuron 2017, 94, 431–446. 10.1016/j.neuron.2017.03.016. - DOI - PMC - PubMed
    1. Bruns R. F.; Mitchell S. N.; Wafford K. A.; Harper A. J.; Shanks E. A.; Carter G.; O’Neill M. J.; Murray T. K.; Eastwood B. J.; Schaus J. M.; Beck J. P.; Hao J.; Witkin J. M.; Li X.; Chernet E.; Katner J. S.; Wang H.; Ryder J. W.; Masquelin M. E.; Thompson L. K.; Love P. L.; Maren D. L.; Falcone J. F.; Menezes M. M.; Zhang L.; Yang C. R.; Svensson K. A. Preclinical profile of a dopamine D1 potentiator suggests therapeutic utility in neurological and psychiatric disorders. Neuropharmacology 2018, 128, 351–365. 10.1016/j.neuropharm.2017.10.032. - DOI - PubMed