Are 5-HT<sub>1</sub> receptor agonists effective anti-migraine drugs?

Tanaka, Masaru; Török, Nóra; Vécsei, László

doi:10.1080/14656566.2021.1910235

Cited by 34 publications

(31 citation statements)

References 12 publications

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“…Importantly, this new, L-KYN-containing peptide displays a strong antinociceptive effect in in vivo tests [123]. It is worth mentioning because of the impact on the serotonin metabolism; the kynurenine pathway was already suggested to be important in migraine attack and under migraine treatment [124,125]. The crosstalk between the kynurenine pathway and tetrahydrobiopterin (BH4) pathway has been recently raised as a very important factor in nociception processes.…”

Section: Therapeutic Potential Of the Kynurenine Pathway In The Treatment Of Neuropathic Painmentioning

confidence: 99%

The Kynurenine Pathway as a Potential Target for Neuropathic Pain Therapy Design: From Basic Research to Clinical Perspectives

Ciapała

Mika

Rojewska

2021

IJMS

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Accumulating evidence suggests the key role of the kynurenine pathway (KP) of the tryptophan metabolism in the pathogenesis of several diseases. Despite extensive research aimed at clarifying the mechanisms underlying the development and maintenance of neuropathic pain, the roles of KP metabolites in this process are still not fully known. Although the function of the peripheral KP has been known for several years, it has only recently been acknowledged that its metabolites within the central nervous system have remarkable consequences related to physiology and behavior. Both the products and metabolites of the KP are involved in the pathogenesis of pain conditions. Apart from the neuroactive properties of kynurenines, the KP regulates several neurotransmitter systems in direct or indirect ways. Some neuroactive metabolites are known to have neuroprotective properties (kynurenic acid, nicotinamide adenine dinucleotide cofactor), while others are toxic (3-hydroxykynurenine, quinolinic acid). Numerous animal models show that modulation of the KP may turn out to be a viable target for the treatment of diseases. Importantly, some compounds that affect KP enzymes are currently described to possess analgesic properties. Additionally, kynurenine metabolites may be useful for assessing response to therapy or as biomarkers in therapeutic monitoring. The following review describes the molecular site of action and changes in the levels of metabolites of the kynurenine pathway in the pathogenesis of various conditions, with a particular emphasis on their involvement in neuropathy. Moreover, the potential clinical implications of KP modulation in chronic pain therapy as well as the directions of new research initiatives are discussed.

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Section: Therapeutic Potential Of the Kynurenine Pathway In The Treatment Of Neuropathic Painmentioning

confidence: 99%

The Kynurenine Pathway as a Potential Target for Neuropathic Pain Therapy Design: From Basic Research to Clinical Perspectives

Ciapała

Mika

Rojewska

2021

IJMS

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“…However, it is worth mentioning that inhibition of IDO activity has some potential in neurological disorder therapy. Recent reports indicate that 1-methyl-tryptophan appears to be a promising agent for migraine and neuropathic pain therapies [209,246].…”

Section: Summary and Therapeutic Perspectivementioning

confidence: 99%

Role of Kynurenine Pathway in Oxidative Stress during Neurodegenerative Disorders

Mor

Tankiewicz-Kwedlo

Krupa

et al. 2021

Cells

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Neurodegenerative disorders are chronic and life-threatening conditions negatively affecting the quality of patients’ lives. They often have a genetic background, but oxidative stress and mitochondrial damage seem to be at least partly responsible for their development. Recent reports indicate that the activation of the kynurenine pathway (KP), caused by an activation of proinflammatory factors accompanying neurodegenerative processes, leads to the accumulation of its neuroactive and pro-oxidative metabolites. This leads to an increase in the oxidative stress level, which increases mitochondrial damage, and disrupts the cellular energy metabolism. This significantly reduces viability and impairs the proper functioning of central nervous system cells and may aggravate symptoms of many psychiatric and neurodegenerative disorders. This suggests that the modulation of KP activity could be effective in alleviating these symptoms. Numerous reports indicate that tryptophan supplementation, inhibition of KP enzymes, and administration or analogs of KP metabolites show promising results in the management of neurodegenerative disorders in animal models. This review gathers and systematizes the knowledge concerning the role of metabolites and enzymes of the KP in the development of oxidative damage within brain cells during neurodegenerative disorders and potential strategies that could reduce the severity of this process.

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“…KYNA was reported to possess antidepressant-like effects and KYNA analogues were described as potential anti-dementia drugs [14,15]. The TRP-KYN pathway is involved in migraine headache and is one of the potential targets as anti-migraine drugs [16]. Modulation of the pathway was found to reduce or prevent substance abuse [17].…”

Section: Introductionmentioning

confidence: 99%

Immune Influencers in Action: Metabolites and Enzymes of the Tryptophan-Kynurenine Metabolic Pathway

et al. 2021

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The tryptophan (TRP)-kynurenine (KYN) metabolic pathway is a main player of TRP metabolism through which more than 95% of TRP is catabolized. The pathway is activated by acute and chronic immune responses leading to a wide range of illnesses including cancer, immune diseases, neurodegenerative diseases and psychiatric disorders. The presence of positive feedback loops facilitates amplifying the immune responses vice versa. The TRP-KYN pathway synthesizes multifarious metabolites including oxidants, antioxidants, neurotoxins, neuroprotectants and immunomodulators. The immunomodulators are known to facilitate the immune system towards a tolerogenic state, resulting in chronic low-grade inflammation (LGI) that is commonly present in obesity, poor nutrition, exposer to chemicals or allergens, prodromal stage of various illnesses and chronic diseases. KYN, kynurenic acid, xanthurenic acid and cinnabarinic acid are aryl hydrocarbon receptor ligands that serve as immunomodulators. Furthermore, TRP-KYN pathway enzymes are known to be activated by the stress hormone cortisol and inflammatory cytokines, and genotypic variants were observed to contribute to inflammation and thus various diseases. The tryptophan 2,3-dioxygenase, the indoleamine 2,3-dioxygenases and the kynurenine-3-monooxygenase are main enzymes in the pathway. This review article discusses the TRP-KYN pathway with special emphasis on its interaction with the immune system and the tolerogenic shift towards chronic LGI and overviews the major symptoms, pro- and anti-inflammatory cytokines and toxic and protective KYNs to explore the linkage between chronic LGI, KYNs, and major psychiatric disorders, including depressive disorder, bipolar disorder, substance use disorder, post-traumatic stress disorder, schizophrenia and autism spectrum disorder.

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Are 5-HT₁ receptor agonists effective anti-migraine drugs?

Cited by 34 publications

References 12 publications

The Kynurenine Pathway as a Potential Target for Neuropathic Pain Therapy Design: From Basic Research to Clinical Perspectives

The Kynurenine Pathway as a Potential Target for Neuropathic Pain Therapy Design: From Basic Research to Clinical Perspectives

Role of Kynurenine Pathway in Oxidative Stress during Neurodegenerative Disorders

Immune Influencers in Action: Metabolites and Enzymes of the Tryptophan-Kynurenine Metabolic Pathway

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Are 5-HT1 receptor agonists effective anti-migraine drugs?

Cited by 34 publications

References 12 publications

The Kynurenine Pathway as a Potential Target for Neuropathic Pain Therapy Design: From Basic Research to Clinical Perspectives

The Kynurenine Pathway as a Potential Target for Neuropathic Pain Therapy Design: From Basic Research to Clinical Perspectives

Role of Kynurenine Pathway in Oxidative Stress during Neurodegenerative Disorders

Immune Influencers in Action: Metabolites and Enzymes of the Tryptophan-Kynurenine Metabolic Pathway

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Are 5-HT₁ receptor agonists effective anti-migraine drugs?