The effects of a novel and selective inhibitor of tryptophan 2,3-dioxygenase on tryptophan and serotonin metabolism in the rat

Biochemical Pharmacology
M SalterD J Madge

Abstract

The effects of a novel inhibitor 680C91 ((E)-6-fluoro-3-[2-(3- pyridyl)vinyl]-1H-indole) of the key enzyme of tryptophan catabolism tryptophan 2,3-dioxygenase (TDO) (EC 1.13.11.11), were examined on tryptophan catabolism in vitro and in vivo and on brain levels of tryptophan, serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA). 680C91 was a potent (Ki = 51 nM) and selective TDO inhibitor with no inhibitory activity against indoleamine 2,3-dioxygenase (EC 1.13.11.17), monoamine oxidase A and B, 5-HT uptake and 5-HT1A,1D,2A and 2C receptors at a concentration of 10 microM. 680C91 had no effect on the binding of tryptophan to serum albumin in plasma and inhibited TDO competitively with respect to its substrate tryptophan. 680C91 inhibited the catabolism of tryptophan by rat liver cells and rat liver perfused in situ. The catabolism of L-[ring-2-14C]-tryptophan and a load dose of tryptophan (100 mg/kg) in vivo were inhibited by prior administration of 680C91. Administration of 680C91 alone produced marked increases in brain tryptophan, 5-HT and 5-HIAA. A load dose of tryptophan (100 mg/kg), producing increases in brain tryptophan 4-fold greater than that seen with 680C91, did not increase brain 5-HT and 5-HIAA to levels greate...Continue Reading

References

May 1, 1977·Journal of Neurochemistry·A YuwilerL Braun
Jan 1, 1978·Progress in Neuro-psychopharmacology·D L MurphyJ L Costa
Jan 29, 1979·Life Sciences·D L Garver, J M Davis
Oct 1, 1976·Archives of General Psychiatry·M AsbergP Thorén
Jan 1, 1992·Physiological Reviews·B L Jacobs, E C Azmitia
Dec 1, 1989·Journal of Neurochemistry·J D Schaechter, R J Wurtman
Nov 15, 1986·The Biochemical Journal·M Salter, C I Pogson
Mar 1, 1973·Journal of Neurochemistry·A TagliamonteG L Gessa
Jan 1, 1982·Psychopharmacology·S E MøllerP Honoré
Jan 1, 1993·Annual Review of Pharmacology and Toxicology·L E Hollister, J L Claghorn

❮ Previous
Next ❯

Citations

Jul 6, 2011·Journal of Medicinal Chemistry·Eduard DolusićRaphaël Frédérick
Feb 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Luc PilotteBenoît J Van den Eynde
Feb 12, 2010·Schizophrenia Bulletin·Ikwunga Wonodi, Robert Schwarcz
Nov 21, 2008·Clinical and Experimental Pharmacology & Physiology·Gillian M MackayL Gail Darlington
Mar 13, 2012·Pharmacological Reviews·Stephanie W WattsSusan M Barman
Oct 21, 2010·American Journal of Physiology. Endocrinology and Metabolism·Leo F DohertyHugh S Taylor
Sep 1, 2012·CNS Oncology·Michael PlattenWolfgang Wick
Jul 25, 2015·Journal of Medicinal Chemistry·Amy B DounayPatrick R Verhoest
Aug 9, 2005·Expert Opinion on Therapeutic Targets·Alexander J MullerGeorge C Prendergast
Dec 6, 2014·Drug Discovery Today·Christopher J D Austin, Louis M Rendina
Apr 21, 2016·Journal of Enzyme Inhibition and Medicinal Chemistry·Georgios PantourisChristopher G Mowat
Feb 19, 2015·Frontiers in Immunology·Nicolas van Baren, Benoît J Van den Eynde
Jan 30, 2015·Frontiers in Immunology·Michael PlattenKatharina Ochs
Apr 27, 2016·Proceedings of the National Academy of Sciences of the United States of America·Carlo BredaFlaviano Giorgini
May 18, 2016·Brain : a Journal of Neurology·Nathaniel S WoodlingKatrin I Andreasson
May 14, 2016·Expert Opinion on Therapeutic Patents·Dénes ZádoriLászló Vécsei
Mar 31, 2017·Medical Oncology·Cheng-Peng YuDa-Ya Luo
Aug 2, 2013·Journal of Psychopharmacology·Abdulla A-B Badawy
Nov 6, 2013·The Journal of Endocrinology·Dang-Dang LiZhan-Peng Yue
Dec 12, 2018·Expert Opinion on Therapeutic Patents·Arina Kozlova, Raphaël Frédérick
Feb 15, 2019·Nature Reviews. Drug Discovery·Michael PlattenChristiane A Opitz
Jul 18, 2018·Metabolic Brain Disease·Yanjie QinYongning Lu
Dec 11, 2019·British Journal of Cancer·Christiane A OpitzSaskia Trump
Dec 5, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Suat SariJóhannes Reynisson
Apr 14, 2016·Metabolic Brain Disease·Cheng-Peng YuDa-Ya Luo
Aug 14, 2015·Cancer Immunology Research·Nicolas van Baren, Benoît J Van den Eynde
Dec 7, 2019·Cancer Immunology Research·Florence SchrammeBenoit J Van den Eynde
Dec 17, 2017·Cancer Research·George C PrendergastAlexander J Muller
Mar 24, 2021·Neurochemical Research·Noura Magdy ThabetEnas Mahmoud Moustafa
Nov 20, 2020·Pharmacology & Therapeutics·Ana DolšakMatej Sova
Apr 27, 2021·Bioorganic & Medicinal Chemistry·Rossella Capochiani de IudicibusLai-Ming Ching
Nov 2, 2021·Expert Opinion on Therapeutic Targets·Fanni Annamária Boros, László Vécsei

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.