Novel Kynurenic Acid Analogues in the Treatment of Migraine and Neurodegenerative Disorders: Preclinical Studies and Pharmaceutical Design

Author(s): Janos Tajti, Zsofia Majlath, Delia Szok, Anett Csati, Jozsef Toldi, Ferenc Fulop, Laszlo Vecsei.

Journal Name: Current Pharmaceutical Design

Volume 21 , Issue 17 , 2015

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Abstract:

Though migraine and neurodegenerative disorders have a high socioeconomic impact, their therapeutic management has not been fully addressed. Their pathomechanisms are not completely understood, but glutamateinduced excitotoxicity, mitochondrial disturbances and oxidative stress all seem to play crucial roles. The overactivation of glutamate receptors contributes to the hyperexcitability observed in migraine and also to the neurodegenerative process. The kynurenine pathway of the tryptophan metabolism produces the only known endogenous Nmethyl- D-aspartate receptor antagonist, kynurenic acid, which has been proven in different preclinical studies to exert a neuroprotective effect. Influencing the kynurenine pathway might be beneficial in migraine and neurodegenerative diseases, and in the normalization of glutamatergic neurotransmission and the prevention of excitotoxic neuronal damage. The synthesis of kynurenic acid analogues may offer a valuable tool for drug development.

Keywords: Migraine, hyperexcitability, neurodegeneration, neuroprotection, kynurenic acid, kynurenic acid analogues.

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Article Details

VOLUME: 21
ISSUE: 17
Year: 2015
Page: [2250 - 2258]
Pages: 9
DOI: 10.2174/1381612821666150105163055
Price: $58

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