Citation

Boros F, Vécsei L. Expert Opin. Investig. Drugs 2020; 29(11): 1223-1247.

Copyright

(Copyright © 2020, Informa Healthcare)

DOI

10.1080/13543784.2020.1813716

PMID

32819186

Abstract

INTRODUCTION: The diverse neuro- and immunomodulatory effects of kynurenine pathway (KP) enzymes and metabolites exert offer possibilities for intervention in diseases such as autoimmunity, neurodegeneration, and neoplastic processes.
AREAS COVERED: This review focuses on data obtained from the preclinical and clinical use of a KP metabolite analog and structurally related compounds. 4-Cl-KYN has completed clinical trials in depression without success. However, the good safety data give hope for further trials in suicide prevention, neuropathic pain, and dyskinesia. Quinoline-3-carboxamide derivatives laquinimod, paquinimod, and tasquinimod show structural similarities to kynurenines. Laquinimod and paquinimod show promising results in the treatment of autoimmune diseases, tasquinimod is considered primarily as an anti-cancer drug. Data available until 31 May 2020 at Clinicaltrials.gov and PubMed have been reviewed.
EXPERT OPINION: The failure of 4-Cl-KYN for use as an anti-depressant may be related to inadequate concentration, or that the ketamine-like rapid anti-depressant effect is not produced via NMDAR modulation. Further clarification may emerge from studies involving higher drug concentration, and/or from identification of ketamine targets. Clinical application trials in very diverse indications of structurally related quinoline-3-carboxamides and the wide range of their mode of action warrant further studies permitting direct comparison of effects and better target identification.

Language: en

Keywords

4-Cl-KYN; Animals; Antineoplastic Agents; autoimmune diseases; Autoimmune Diseases; Drug Development; Humans; Kynurenine; kynurenine pathway; laquinimod; Neoplasms; Neurodegenerative Diseases; nmdar antagonist; paquinimod; quinoline-3-carboxamides; Quinolines; tasquinimod