Determination of the Norepinephrine Level by High-Performance Liquid Chromatography to Assess the Protective Effect of MAO-B Inhibitors Against DSP-4 Toxicity

Haberle, D.; Magyar, K.; Szökő, Éva

doi:10.1093/chromsci/40.9.495

Cited by 8 publications

(3 citation statements)

References 27 publications

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“…Rasagiline, which is more potent inhibitor of MAO-B, than (-)-deprenyl, but without uptake inhibitory potency ( Table 1) in doses of 1 to 10 mg/kg, was not able to prevent DSP-4 toxicity ( Fig. 1) [61].…”

Section: Table 1 Monoamine Uptake Inhibition By Deprenyl and Its Metmentioning

confidence: 98%

Pharmacological Aspects of (-)-Deprenyl

Magyar¹,

Pálfi²,

Tábi³

et al. 2004

Current Medicinal Chemistry

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Deprenyl, the selective irreversible inhibitor of monoamine oxidase-B (MAO-B), has been synthesised as a potential antidepressant, however, due to its dopamine potentiating capacity, became a registered drug in the treatment of Parkinson's disease. Deprenyl possesses a wide range of pharmacological activities; some of them are not related to its MAO-B inhibitory potency. Beside its dopamine potentiating effect, it renders protection against a number of dopaminergic, cholinergic and noradrenergic neurotoxins with a complex mechanism of action. By inducing antioxidant enzymes and decreasing the formation of reactive oxygen species, deprenyl is able to combat an oxidative challenge implicated as a common causative factor in neurodegenerative diseases. In a dose substantially lower than required for MAO-B inhibition (10(-9)-10(-13) M), deprenyl interferes with early apoptotic signalling events induced by various kinds of insults in cell cultures of neuroectodermal origin, thus protecting cells from apoptotic death. Deprenyl requires metabolic conversion to a hitherto unidentified metabolite to exert its antiapoptotic effect, which serves to protect the integrity of the mitochondrion by inducing transcriptional and translational changes. Pharmacokinetic and metabolism studies have revealed that deprenyl undergoes intensive first pass metabolism, and its major metabolites also possess pharmacological activities. The ratio of the parent compound and its metabolites reaching the systemic circulation and the brain are highly dependent on the routes of administration. Therefore, in the treatment of neurodegenerative diseases, reconsideration of the dosing schedule, by lowering the dose of deprenyl and choosing the most appropriate route of administration, would diminish undesired adverse effects, with unaltered neuroprotective potency.

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Section: Table 1 Monoamine Uptake Inhibition By Deprenyl and Its Metmentioning

confidence: 98%

Pharmacological Aspects of (-)-Deprenyl

Magyar¹,

Pálfi²,

Tábi³

et al. 2004

Current Medicinal Chemistry

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“…To reduce variability, a single researcher measured tumor volume through all the 105 K-based assays. The applied doses of drugs or compounds were based on those used in previous animal studies (Haberle et al, 2002;Francis et al, 2012;Ledesma et al, 2014;Cheng et al, 2016;Chen et al, 2017). The drugs were administrated as follows: vehicle control (0.2% carboxymethylcellulose (CMC) and 0.25% Tween-80; intraperitoneal), rapamycin (1 or 0.25 mg/kg/day in CMC; intraperitoneal), clorgyline (10 mg/kg/day in saline; intraperitoneal), loratadine (25 mg/kg/day in CMC; oral), and rasagiline (1 mg/kg/day in saline; intraperitoneal).…”

Section: In Vivo Assaysmentioning

confidence: 99%

Histamine signaling and metabolism identify potential biomarkers and therapies for lymphangioleiomyomatosis

et al. 2021

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Inhibition of mTOR is the standard of care for lymphangioleiomyomatosis (LAM). However, this therapy has variable tolerability and some patients show progressive decline of lung function despite treatment. LAM diagnosis and monitoring can also be challenging due to the heterogeneity of symptoms and insufficiency of noninvasive tests. Here, we propose monoamine-derived biomarkers that provide preclinical evidence for novel therapeutic approaches. The major histamine-derived metabolite methylimidazoleacetic acid (MIAA) is relatively more abundant in LAM plasma, and MIAA values are independent of VEGF-D. Higher levels of histamine are associated with poorer lung function and greater disease burden. Molecular and cellular analyses, and metabolic profiling confirmed active histamine signaling and metabolism. LAM tumorigenesis is reduced using approved drugs targeting monoamine oxidases A/B (clorgyline and rasagiline) or histamine H1 receptor (loratadine), and loratadine synergizes with rapamycin. Depletion of Maoa or Hrh1 expression, and administration of an L-histidine analog, or a low L-histidine diet, also reduce LAM tumorigenesis. These findings extend our knowledge of LAM biology and suggest possible ways of improving disease management.

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“…Literature survey reveals that only a few methods were reported for quantification of Rasagiline in human plasma and pharmaceutical analysis [5–9] . These include HPLC [5] , [6] , crystallographic analysis [7] , and LC-MS/MS [8,9] . Only two methods were reported for quantification of Rasagiline in human plasma with LC-MS/MS [8,9] .…”

Section: Introductionmentioning

confidence: 99%

Bio-analytical method development and validation of Rasagiline by high performance liquid chromatography tandem mass spectrometry detection and its application to pharmacokinetic study

Konda

Chandu²,

Challa

et al. 2012

Journal of Pharmaceutical Analysis

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The most suitable bio-analytical method based on liquid–liquid extraction has been developed and validated for quantification of Rasagiline in human plasma. Rasagiline-13C3 mesylate was used as an internal standard for Rasagiline. Zorbax Eclipse Plus C18 (2.1 mm×50 mm, 3.5 μm) column provided chromatographic separation of analyte followed by detection with mass spectrometry. The method involved simple isocratic chromatographic condition and mass spectrometric detection in the positive ionization mode using an API-4000 system. The total run time was 3.0 min. The proposed method has been validated with the linear range of 5–12000 pg/mL for Rasagiline. The intra-run and inter-run precision values were within 1.3%–2.9% and 1.6%–2.2% respectively for Rasagiline. The overall recovery for Rasagiline and Rasagiline-13C3 mesylate analog was 96.9% and 96.7% respectively. This validated method was successfully applied to the bioequivalence and pharmacokinetic study of human volunteers under fasting condition.

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Determination of the Norepinephrine Level by High-Performance Liquid Chromatography to Assess the Protective Effect of MAO-B Inhibitors Against DSP-4 Toxicity

Cited by 8 publications

References 27 publications

Pharmacological Aspects of (-)-Deprenyl

Pharmacological Aspects of (-)-Deprenyl

Histamine signaling and metabolism identify potential biomarkers and therapies for lymphangioleiomyomatosis

Bio-analytical method development and validation of Rasagiline by high performance liquid chromatography tandem mass spectrometry detection and its application to pharmacokinetic study

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