Determination of tenilsetam in human plasma and urine by high-performance liquid chromatography

Burrows, Jennifer; Coppin, Frédéric

doi:10.1016/s0378-4347(00)83859-1

Cited by 3 publications

(2 citation statements)

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“…In vivo , Tenilsetam has been assayed in human plasma and urine, where recovery in both media was achieved with endogenous background material separated accurately via a HPLC method [82]. Several pharmacokinetic studies were completed and plasma concentrations were observed over 72 h period.…”

Section: Potential Anti-inflammatory Drug Candidates For the Treatmentioning

confidence: 99%

Chronic Neuroinflammation in Alzheimer’s Disease: New Perspectives on Animal Models and Promising Candidate Drugs

Millington

Sonego

Karunaweera

et al. 2014

BioMed Research International

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Chronic neuroinflammation is now considered one of the major factors in the pathogenesis of Alzheimer's disease (AD). However, the most widely used transgenic AD models (overexpressing mutated forms of amyloid precursor protein, presenilin, and/or tau) do not demonstrate the degree of inflammation, neurodegeneration (particularly of the cholinergic system), and cognitive decline that is comparable with the human disease. Hence a more suitable animal model is needed to more closely mimic the resulting cognitive decline and memory loss in humans in order to investigate the effects of neuroinflammation on neurodegeneration. One of these models is the glial fibrillary acidic protein-interleukin 6 (GFAP-IL6) mouse, in which chronic neuroinflammation triggered constitutive expression of the cytokine interleukin-6 (IL-6) in astrocytes. These transgenic mice show substantial and progressive neurodegeneration as well as a decline in motor skills and cognitive function, starting from 6 months of age. This animal model could serve as an excellent tool for drug discovery and validation in vivo. In this review, we have also selected three potential anti-inflammatory drugs, curcumin, apigenin, and tenilsetam, as candidate drugs, which could be tested in this model.

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Section: Potential Anti-inflammatory Drug Candidates For the Treatmentioning

confidence: 99%

Chronic Neuroinflammation in Alzheimer’s Disease: New Perspectives on Animal Models and Promising Candidate Drugs

Millington

Sonego

Karunaweera

et al. 2014

BioMed Research International

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“…Retinalv ascular preparations were performed as described (12,25)and acellular capillaries and pericyte numberswere determinedbytwo observers blindedtothe identity of the samples. Tenilsetamconcentration in the serum of treateddiabetic animal wasmeasured by HPLC exactly as described (26).…”

Section: Experimental Diabeticretinopathymentioning

confidence: 99%

Tenilsetam prevents early diabetic retinopathy without correcting pericyte loss

Hoffmann¹,

Alt²,

Lin

et al. 2006

Thromb Haemost

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Hyperglycemia-induced mitochondrial overproduction of reactive oxygen species leads to the activation of different biochemical pathways involved in endothelial damage of the diabetic retina. Tenilsetam [(+/-)-3-(2-thienyl)-2-piperazinone] is a dicarbonyl scavenger in the millimolar range and a transition metal ion chelator in the micromolar range. We tested its effect on experimental diabetic retinopathy, and on endothelial cell characteristics in vitro. Streptozotocin diabetic male Wistar rats (60 mg/kg BW) received 50 mg/kg BW tenilsetam (D-T) for 36 weeks, or no treatment (D). The impact of tenilsetam (0-30 mM) on endothelial proliferation, apoptosis, sprouting, cytokine-induced leucocyte-endothelial interaction, and VEGF expression was tested in vitro. Tenilsetam did not affect glycemic control or body weight in diabetic animals. The 3.7 fold increase in acellular capillaries in diabetic rats [p < 0.001 vs. non-diabetic controls (N)] was reduced by 70% (p < 0.001) through treatment, but pericyte loss (D vs. N -33%; p < 0.001) remained unaffected. In vitro, tenilsetam inhibited endothelial proliferation at lower doses, while inducing apoptosis at high doses. Leucocyte adhesion was only inhibited at high doses. Sprouting angiogenesis of bovine retinal endothelial cells was promoted at lower doses (< or = 10 mM). At micromolar concentrations, endothelial VEGF expression was upregulated by 100%. Long-term treatment with the AGE-inhibitor and iron-chelating compound tenilsetam inhibits the formation of acellular capillaries without correcting pericyte loss. The compound has dose-dependent effects on endothelial cell function. These data suggest that, independent of known properties, tenilsetam shows important rescue functions on endothelial cells which could be useful for the treatment of early diabetic retinopathy.

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Chelating Activity of Advanced Glycation End-product Inhibitors

Price

Rhett

Thorpe

et al. 2001

Journal of Biological Chemistry

287

205

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The advanced glycation end-product (AGE) hypothesis proposes that accelerated chemical modification of proteins by glucose during hyperglycemia contributes to the pathogenesis of diabetic complications. The two most commonly measured AGEs, N ⑀ -(carboxymethyl)lysine and pentosidine, are glycoxidation products, formed from glucose by sequential glycation and autoxidation reactions. Although several compounds have been developed as AGE inhibitors and are being tested in animal models of diabetes and in clinical trials, the mechanism of action of these inhibitors is poorly understood. In general, they are thought to function as nucleophilic traps for reactive carbonyl intermediates in the formation of AGEs; however alternative mechanisms of actions, such as chelation, have not been rigorously examined. To distinguish between the carbonyl trapping and antioxidant activity of AGE inhibitors, we have measured the chelating activity of the inhibitors by determining the concentration required for 50% inhibition of the rate of copper-catalyzed autoxidation of ascorbic acid in phosphate buffer. All AGE inhibitors studied were chelators of copper, as measured by inhibition of metalcatalyzed autoxidation of ascorbate. Apparent binding constants for copper ranged from ϳ2 mM for aminoguanidine and pyridoxamine, to 10 -100 M for carnosine, phenazinediamine, OPB-9195 and tenilsetam. The AGE-breakers, phenacylthiazolium and phenacyldimethylthiazolium bromide, and their hydrolysis products, were among the most potent inhibitors of ascorbate oxidation. We conclude that, at millimolar concentrations of AGE inhibitors used in many in vitro studies, inhibition of AGE formation results primarily from the chelating or antioxidant activity of the AGE inhibitors, rather than their carbonyl trapping activity. Further, at therapeutic concentrations, the chelating activity of AGE inhibitors and AGE-breakers may contribute to their inhibition of AGE formation and protection against development of diabetic complications.The Maillard or browning reaction between sugars and proteins leads to the formation of chemical modifications and cross-links in proteins, known as advanced glycation end-products (AGEs) 1 (1). These products contribute to the age-dependent chemical modification of long lived tissue proteins (2), and accelerated formation of AGEs during hyperglycemia is implicated in the development of diabetic complications (1, 2). Consistent with the AGE hypothesis, AGE inhibitors, such as aminoguanidine (AG) (3) and pyridoxamine (PM) (4), inhibit the formation of AGEs in various proteins in vitro and in collagen in vivo (5, 6) and retard the development of diabetic complications in animal models. The two most commonly measured AGEs, N ⑀ -(carboxymethyl)lysine (CML) and pentosidine, are glycoxidation products formed by sequential glycation and oxidation reactions (7), and traces of transition metal ions in physiological buffers are potent catalysts of the formation of these AGEs in vitro (8). AGE inhibitors are nucleophilic compounds design...

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Determination of tenilsetam in human plasma and urine by high-performance liquid chromatography

Cited by 3 publications

References 1 publication

Chronic Neuroinflammation in Alzheimer’s Disease: New Perspectives on Animal Models and Promising Candidate Drugs

Chronic Neuroinflammation in Alzheimer’s Disease: New Perspectives on Animal Models and Promising Candidate Drugs

Tenilsetam prevents early diabetic retinopathy without correcting pericyte loss

Chelating Activity of Advanced Glycation End-product Inhibitors

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