Dual-acting agents for improving cognition and real-world function in Alzheimer's disease: Focus on 5-HT6 and D3 receptors as hubs.

Neuropharmacology
Mark J MillanKevin C F Fone

Abstract

To date, there are no interventions that impede the inexorable progression of Alzheimer's disease (AD), and currently-available drugs cholinesterase (AChE) inhibitors and the N-Methyl-d-Aspartate receptor antagonist, memantine, offer only modest symptomatic benefit. Moreover, a range of mechanistically-diverse agents (glutamatergic, histaminergic, monoaminergic, cholinergic) have disappointed in clinical trials, alone and/or in association with AChE inhibitors. This includes serotonin (5-HT) receptor-6 antagonists, despite compelling preclinical observations in rodents and primates suggesting a positive influence on cognition. The emphasis has so far been on high selectivity. However, for a multi-factorial disorder like idiopathic AD, 5-HT6 antagonists possessing additional pharmacological actions might be more effective, by analogy to "multi-target" antipsychotics. Based on this notion, drug discovery programmes have coupled 5-HT6 blockade to 5-HT4 agonism and inhibition of AchE. Further, combined 5-HT6/dopamine D3 receptor (D3) antagonists are of especial interest since D3 blockade mirrors 5-HT6 antagonism in exerting broad-based pro-cognitive properties in animals. Moreover, 5-HT6 and dopamine D3 antagonists promote neurocog...Continue Reading

References

Oct 23, 2003·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Andrew G FoleyCiaran M Regan
Jan 20, 2004·Journal of Chemical Neuroanatomy·Jean-Pierre Hornung
Aug 24, 2006·The International Journal of Neuropsychopharmacology·Benjamin Di CaraMark J Millan
Oct 24, 2006·Journal of Neurochemistry·Cornelis J Van der SchyfMoussa B H Youdim
Dec 26, 2006·The Journal of Biological Chemistry·Hyung-Mun YunHyewhon Rhim
Jul 4, 2008·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Virginie Da Silva CostaFrançois Dauphin
Aug 5, 2008·Trends in Pharmacological Sciences·Mark J MillanClotilde Mannoury la Cour
Sep 17, 2008·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Florence Loiseau, Mark J Millan
Dec 17, 2008·Trends in Pharmacological Sciences·Madeleine V KingKevin C F Fone
Feb 4, 2010·Parkinsonism & Related Disorders·Roberto MaggioMark J Millan
Feb 13, 2010·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Vincenzo MicaleFilippo Drago
Feb 20, 2010·Current Topics in Medicinal Chemistry·Richard A GlennonMałgorzata Dukat
Jul 16, 2010·Psychopharmacology·Ji-Kyung ChoiBruce G Jenkins
Jul 29, 2010·The International Journal of Neuropsychopharmacology·Mark J MillanJay S Schneider
Aug 6, 2010·Journal of Receptor and Signal Transduction Research·Cristina MissalePierFranco Spano
Feb 19, 2011·Current Opinion in Pharmacology·Xabier CodonyMaria Javier Ramírez
Mar 30, 2011·Behavioural Brain Research·Virginie Da Silva Costa-AzeMichel Boulouard
Jun 22, 2011·Cerebral Cortex·Pascal FossatJean-Pierre Mothet
Oct 28, 2011·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·David J G WatsonKevin C F Fone
Jan 10, 2012·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Christine A ParkerLaurent Martarello

❮ Previous
Next ❯

Citations

Jun 3, 2021·Biomolecules·Philippe De Deurwaerdère, Abdeslam Chagraoui
Jul 27, 2021·Bioorganic & Medicinal Chemistry Letters·Katarzyna Kucwaj-BryszJadwiga Handzlik
Oct 3, 2020·Neuropharmacology·Giuseppe Di Giovanni, Philippe De Deurwaerdère

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Aging

This feed focuses on cellular aging with emphasis on mitochondria, autophagy, and metabolic processes associated with aging and longevity. Here is the latest research on cell aging.

Cell Aging (Keystone)

This feed focuses on cellular aging with emphasis on the mitochondria, autophagy, and metabolic processes associated with aging and longevity. Here is the latest research on cell aging.

Antipsychotic Drugs

Antipsychotic drugs are a class of medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia and bipolar disorder. Discover the latest research on antipsychotic drugs here

Related Papers

Pharmacology & Therapeutics
Ellen S Mitchell, John F Neumaier
Current Topics in Medicinal Chemistry
Werner J Geldenhuys, Cornelis J Van der Schyf
Current Opinion in Pharmacology
Xabier CodonyMaría Javier Ramírez
Current Opinion in Investigational Drugs
C Reavill, D C Rogers
© 2022 Meta ULC. All rights reserved