Allosteric Modulators of G Protein-Coupled Dopamine and Serotonin Receptors: A New Class of Atypical Antipsychotics

Pharmaceuticals
Irene FascianiMario Rossi

Abstract

Schizophrenia was first described by Emil Krapelin in the 19th century as one of the major mental illnesses causing disability worldwide. Since the introduction of chlorpromazine in 1952, strategies aimed at modifying the activity of dopamine receptors have played a major role for the treatment of schizophrenia. The introduction of atypical antipsychotics with clozapine broadened the range of potential targets for the treatment of this psychiatric disease, as they also modify the activity of the serotoninergic receptors. Interestingly, all marketed drugs for schizophrenia bind to the orthosteric binding pocket of the receptor as competitive antagonists or partial agonists. In recent years, a strong effort to develop allosteric modulators as potential therapeutic agents for schizophrenia was made, mainly for the several advantages in their use. In particular, the allosteric binding sites are topographically distinct from the orthosteric pockets, and thus drugs targeting these sites have a higher degree of receptor subunit specificity. Moreover, "pure" allosteric modulators maintain the temporal and spatial fidelity of native orthosteric ligand. Furthermore, allosteric modulators have a "ceiling effect", and their modulatory effe...Continue Reading

References

Mar 1, 1972·Proceedings of the National Academy of Sciences of the United States of America·J H Brown, M H Makman
Sep 29, 1980·Brain Research·E StefaniniP F Spano
Jul 23, 1996·Proceedings of the National Academy of Sciences of the United States of America·J P Huidobro-Toro, R A Harris
May 1, 1997·Journal of Neurochemistry·J A Schetz, D R Sibley
Jan 24, 1998·Naunyn-Schmiedeberg's Archives of Pharmacology·J F López-GiménezM T Vilaró
Feb 12, 1998·Proceedings of the National Academy of Sciences of the United States of America·R A Lerner
Feb 12, 1998·Proceedings of the National Academy of Sciences of the United States of America·E A ThomasJ G Sutcliffe
Feb 11, 1998·Physiological Reviews·C MissaleM G Caron
May 26, 1998·Psychopharmacology·C T EganM Teitler
Jul 11, 1998·The American Journal of Psychiatry·S KapurS Houle
May 25, 2001·The Journal of Biological Chemistry·M ScarselliR Maggio
Dec 26, 2001·The Journal of Pharmacology and Experimental Therapeutics·H MöhlerU Rudolph
Jan 25, 2002·Annual Review of Pharmacology and Toxicology·Guochuan Tsai, Joseph T Coyle
Jun 20, 2003·Molecular Pharmacology·Wha Bin ImDac M Dinh
Aug 16, 2003·The Journal of Biological Chemistry·Juan J CarrilloGraeme Milligan
Dec 4, 2003·Progress in Neuro-psychopharmacology & Biological Psychiatry·Herbert Y MeltzerJunji Ichikawa
Apr 2, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Philippe De DeurwaerdèreUmberto Spampinato
May 1, 2004·Psychopharmacology·Patricia S Goldman-RakicGraham V Williams
May 26, 2004·The Journal of Biological Chemistry·Samuel P LeeSusan R George
Aug 30, 2005·The Journal of Pharmacology and Experimental Therapeutics·Vaneeta VermaRam K Mishra
Jan 13, 2006·British Journal of Pharmacology·Anna M LewandowiczJarmo T Laitinen
Jan 26, 2006·Annals of Clinical Psychiatry : Official Journal of the American Academy of Clinical Psychiatrists·Francisco López-MuñozGabriel Rubio
Oct 26, 2006·The Journal of Pharmacology and Experimental Therapeutics·Mario RossiRoberto Maggio
Oct 27, 2006·European Journal of Pharmacology·Benita SjögrenPer Svenningsson
Nov 4, 2006·Journal of Proteome Research·Luigi F AgnatiKjell Fuxe
Jan 26, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Neil M RichtandRobert K McNamara
Mar 22, 2007·Movement Disorders : Official Journal of the Movement Disorder Society·Regina KatzenschlagerAndrew J Lees
Apr 6, 2007·Trends in Neurosciences·Anders Björklund, Stephen B Dunnett

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Jun 12, 2021·Frontiers in Cell and Developmental Biology·Dianne M Perez

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