Therapeutic utility of NK3 receptor antagonists for the treatment of schizophrenia

Current Pharmaceutical Design
Lee A Dawson, Paul W Smith

Abstract

The dopaminergic and glutamatergic hypotheses dominate current drug discovery strategies. The dopamine hypothesis states that hyperactivity of the mesolimbic dopaminergic pathway is associated with positive symptoms of the disease, whereas hypoactivity of the mesocortical dopaminergic pathway is associated with the negative and cognitive symptoms. Increasing evidence has also suggested that hypoactivity in the corticolimbic glutamatergic system may contribute to the complex interplay between dysfunctional aspects of these neurotransmitter systems, which could account for much of the symptomatology observed in schizophrenia. Current antipsychotic drugs display moderate efficacy in treating the positive symptoms and limited efficacy against the negative, cognitive, or co-morbidity symptoms of the disease. They are also associated with significant side effects such as extrapyramidal side effects and metabolic disturbances. Thus pharmacologies that are able to more selectively modulate the underlying neuronal substrates of schizophrenia may have utility as efficacious and wide spectrum antipsychotic therapies with potentially improved side effect liabilities. The neuropeptide neuromodulator/neurotransmitter class and their associat...Continue Reading

Citations

Mar 23, 2011·Expert Opinion on Therapeutic Patents·Pari MalherbeHassen Ratni
Jul 27, 2010·Schizophrenia Research·Rajiv TandonMatcheri S Keshavan
Mar 30, 2017·Inflammopharmacology·Anil KumarDinesh K Dhull
May 19, 2012·Nature Reviews. Drug Discovery·Guy Griebel, Florian Holsboer
Sep 14, 2018·Current Medicinal Chemistry·Charlene Gadais, Steven Ballet
Jan 1, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sekoni D NoelUrsula B Kaiser
Jan 4, 2019·Nature Communications·Jendrik SchöppeAndreas Plückthun
Dec 4, 2019·Neuroscience and Biobehavioral Reviews·Benjamín RodríguezMirian A F Hayashi
Sep 21, 2010·Bioorganic & Medicinal Chemistry Letters·Hassen RatniWill Spooren
Jun 6, 2014·ACS Medicinal Chemistry Letters·Stephen HanessianGuillaume De Nanteuil

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