Time-course of kynurenic acid concentration in mouse serum following the administration of a novel kynurenic acid analog

Zádori, Dénes; Ilisz, István; Klivényi, Péter; Szatmári, István; Fülöp, Ferenc; Toldi, József; Vécsei, László; Péter, Antal

doi:10.1016/j.jpba.2011.02.014

Cited by 15 publications

(13 citation statements)

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“…Previous studies suggested that KYNA amides exert their effect, similarly to KYNA (34), via an interaction with glutamate activity, although no direct evidence was reported. However, one possibility is that KYNA amides can dissociate into KYNA (35), which is known to block the glycine site of NMDA receptors (26). Though in previous studies MK801 has shown an anti-nociceptive effect on phase II of the plantar formalin test, in this study KYNA-A1 showed a significant anti-hyperalgesic effect in the same phase only in the presence of NTG.…”

Section: Discussionmentioning

confidence: 99%

Effects of kynurenic acid analogue 1 (KYNA-A1) in nitroglycerin-induced hyperalgesia: Targets and anti-migraine mechanisms

et al. 2016

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Background: Trigeminal sensitization represents a major mechanism underlying migraine attacks and their recurrence. Nitroglycerin (NTG) administration provokes spontaneous migraine-like headaches and in rat, an increased sensitivity to the formalin test. Kynurenic acid (KYNA), an endogenous regulator of glutamate activity and its analogues attenuate NTG-induced neuronal activation in the nucleus trigeminalis caudalis (NTC). The anti-hyperalgesic effect of KYNA analogue 1 (KYNA-A1) was investigated on animal models specific for migraine pain. Aim: Rats made hyperalgesic by NTG administration underwent the plantar or orofacial formalin tests. The effect of KYNA-A1 was evaluated in terms of nocifensive behavior and of neuronal nitric oxide synthase (nNOS), calcitonin generelated peptide (CGRP) and cytokines expression in areas involved in trigeminal nociception. Results: KYNA-A1 abolished NTG-induced hyperalgesia in both pain models; NTG alone or associated to formalin injection induced an increased mRNA expression of CGRP, nNOS and cytokines in the trigeminal ganglia and central areas, which was reduced by KYNA-A1. Additionally, NTG caused a significant increase in nNOS immunoreactivity in the NTC, which was prevented by KYNA-A1. Conclusion: Glutamate activity is likely involved in mediating hyperalgesia in an animal model specific for migraine. Its inhibition by means of a KYNA analogue modulates nNOS, CGRP and cytokines expression at peripheral and central levels.

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Section: Discussionmentioning

confidence: 99%

Effects of kynurenic acid analogue 1 (KYNA-A1) in nitroglycerin-induced hyperalgesia: Targets and anti-migraine mechanisms

et al. 2016

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“…To date there has been only one study of the pharmacokinetic properties of KYNA amides, which found that only a small proportion of KA-1 decays into KYNA in the serum of C57B/6 mice (Zádori et al, 2011a).…”

Section: Discussionmentioning

confidence: 99%

“…The KYNA amides serve as prodrugs and dissociate into KYNA, which can exert its pharmacological effects. With regard to the clarification of this issue, only one pharmacokinetic study is available to date (Zádori et al, 2011a). In that study, KYNA and KA-1 levels were measured with high-performance liquid chromatography (HPLC) in C57B/6 mouse serum following the intraperitoneal administration of KA-1.…”

Section: Introductionmentioning

confidence: 99%

A comparative assessment of two kynurenic acid analogs in the formalin model of trigeminal activation: a behavioral, immunohistochemical and pharmacokinetic study

et al. 2016

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Abstract:Kynurenic acid (KYNA) has well-established protective properties against glutamatergic neurotransmission, which plays an essential role in the activation and sensitization process during headache disorders. The goal of this study was to Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporationcompare the effects of two KYNA analogs, N-(2-N,N-dimethylaminoethyl)-4-oxo-1H-quinoline-2-carboxamide hydrochloride (KA-1) and N-(2-N-pyrrolidinylethyl)-4-oxo-1H-quinoline-2-carboxamide hydrochloride (KA-2), in the orofacial formalin test of trigeminal pain. Following pretreatment with KA-1 or KA-2, rats were injected with subcutaneous formalin solution in the right whisker pad. Thereafter, the rubbing activity and c-Fos immunoreactivity changes in the spinal trigeminal nucleus pars caudalis (TNC) were investigated. To obtain pharmacokinetic data, KA-1, KA-2 and KYNA concentrations were measured following KA-1 or KA-2 injection. Behavioral tests demonstrated that KA-2 induced a larger amelioration of formalin-evoked alterations as compared with KA-1 and the assessment of c-Fos immunoreactivity in the TNC yielded similar results. Although KA-1 treatment resulted in approximately four times larger area under the curve values in the serum relative to KA-2, the latter resulted in a higher KYNA elevation than in the case of KA-1. With regard to TNC, the concentration of KA-1 was under the limit of detection, while that of KA-2 was quite small and there was no major difference in the approximately 10-fold KYNA elevations. These findings indicate that the differences between the beneficial effects of KA-1 and KA-2 may be explained by the markedly higher peripheral KYNA levels following KA-2 pretreatment. Targeting the peripheral component of trigeminal pain processing would provide an option for drug design which might prove beneficial in headache conditions. Powered by Editorial Manager® and ProduXion Manager® from Aries Systems CorporationReviewer #2: The Authors have tried to address the comments of the referees and partially improved the manuscript. Some issues still need improvement.The sentence 'glutamatergic neurotransmission, which plays an essential role in the activation and sensitization process during headache disorders' is incorrect. This statement may be true for some primary headaches (migraine and chronic migraine), but not for 'headaches' in general.The sentence was modified accordingly.The way the data are presented is still quite confusing:Description of the time boundaries for Phase I and II is missing in the Methods section. The Methods section was supplemented with the requested information.A Figure ( Table 1 reports the levels of significance for data presented in Figure 2: the table should be inglobated in said figure otherwise the reader is forced to go back and forth.The requested modification was done in Figure 2 and Table 1 was removed. Table 2 should be associated to a figure that illustrates mean+sd of time spent in rubbing during the 2 phases of formalin in the di...

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“…Shell particles are a relatively recent trend in chromatographic separation, but several pharmaceutical-bioanalytical [105][106][107][108][109][110][111][112][113][114][115][116][117][118], food analytical [119][120][121][122][123][124][125][126][127][128][129], environmental [130][131][132][133][134] and multidimensional [135][136][137] separations can be found in the literature. Very recently, new commercially available wide-pore stationary phases demonstrate exceptional efficiency for protein separations [138][139][140].…”

Section: Superficially Porous Particlesmentioning

confidence: 99%

Evolution and Current Trends in Liquid and Supercritical Fluid Chromatography

Fekete¹,

Perrenoud²,

Guillarme

2014

CCHG

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Abstract:The current trend in high performance liquid chromatography (HPLC) tends toward the achievement of higher separation efficiency and shorter analysis time. Indeed, better performance in LC has become increasingly important in recent years mainly driven by the challenges of either analyzing more complex samples or increasing the numbers of samples per time unit. In the recent development of particle technology, the use of fully porous sub-2 m particles and sub-3 m shell particles have received considerable attention. Beside packed columns, the new generation of silica-based monolithic columns also offers very high separation power. However, to take full advantage of these innovative phases, the chromatographic system has also to be drastically optimized in terms of upper pressure limit and system volume.This revolution in column technology now spreads and covers several modes of liquid chromatography such as reversedphase liquid chromatography (RPLC), hydrophilic interaction liquid chromatography (HILIC), or even supercritical fluid chromatography (SFC). The HILIC and SFC, which can be considered as alternative modes of chromatography, could also be useful to extend the applicability of chromatography towards the analysis of very hydrophilic and lipophilic compounds, respectively.The present review gives an insight about the theory behind the success of current column technology and presents a summary of latest applications, using various modes of one-dimensional chromatography (RPLC, HILIC, SFC). This paper also shows that theoretically expected column efficiency could sometimes be compromised in practical work especially in the case of narrow bore columns.

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Time-course of kynurenic acid concentration in mouse serum following the administration of a novel kynurenic acid analog

Cited by 15 publications

References 29 publications

Effects of kynurenic acid analogue 1 (KYNA-A1) in nitroglycerin-induced hyperalgesia: Targets and anti-migraine mechanisms

Effects of kynurenic acid analogue 1 (KYNA-A1) in nitroglycerin-induced hyperalgesia: Targets and anti-migraine mechanisms

A comparative assessment of two kynurenic acid analogs in the formalin model of trigeminal activation: a behavioral, immunohistochemical and pharmacokinetic study

Evolution and Current Trends in Liquid and Supercritical Fluid Chromatography

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