Dopamine D2 Receptors Dimers: How can we Pharmacologically Target Them?

Current Neuropharmacology
Marco CarliMarco Scarselli

Abstract

Dopamine D2 and D3 receptors can form homo- and heterodimers and are important targets in Schizophrenia and Parkinson's. Recently, many efforts have been made to pharmacologically target these receptor complexes. This review focuses on various strategies to act specifically on dopamine receptor dimers, that are transiently formed. Various binding and functional assays were reviewed to study the properties of bivalent ligands, particularly for the dualsteric compound SB269,652. The dimerization of D2 and D3 receptors were analyzed by using single particle tracking microscopy. The specific targeting of dopamine D2 and D3 dimers can be achieved with bifunctional ligands, composed of two pharmacophores binding the two orthosteric sites of the dimeric complex. If the target is a homodimer, then the ligand is homobivalent. Instead, if the target is a heterodimer, then the ligand is heterobivalent. However, there is some concern regarding pharmacokinetics and binding properties of such drugs. Recently, a new generation of bitopic compounds with dualsteric properties have been discovered that bind to the orthosteric and the allosteric sites in one monomeric receptor. Regarding dopamine D2 and D3 receptors, a new dualsteric molecule SB2...Continue Reading

Citations

May 31, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Metehan IlterOzge Sensoy
Aug 9, 2020·Frontiers in Pharmacology·Jean Claude Martel, Silvia Gatti McArthur
Mar 24, 2020·Letters in Drug Design & Discovery·Mark Gallant FultonCraig William Lindsley
Aug 15, 2018·Journal of Medicinal Chemistry·Eric A WoldJia Zhou

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