Academic literature on the topic 'Glycinexylidide'

Background Lidocaine exerts antinociceptive effects when applied systemically. The mechanisms are not fully understood but glycinergic mechanisms might be involved. The synaptic glycine concentration is controlled by glycine transporters. Whereas neurons express two types of glycine transporters, astrocytes specifically express glycine transporter 1 (GlyT1). This study focuses on effects of lidocaine and its major metabolites on GlyT1 function. Methods The effects of lidocaine and its metabolites monoethylglycinexylidide (MEGX), glycinexylidide, and N-ethylglycine on GlyT1 function were investigated in uptake experiments with [¹⁴C]-labeled glycine in primary rat astrocytes. Furthermore, the effect of lidocaine and its metabolites on glycine-induced currents were investigated in GlyT1-expressing Xenopus laevis oocytes. Results Lidocaine reduced glycine uptake only at toxic concentrations. The metabolites MEGX, glycinexylidide, and N-ethylglycine, however, significantly reduced glycine uptake (P < 0.05). Inhibition of glycine uptake by a combination of lidocaine with its metabolites at a clinically relevant concentration was diminished with increasing extracellular glycine concentrations. Detailed analysis revealed that MEGX inhibits GlyT1 function (P < 0.05), whereas N-ethylglycine was identified as an alternative GlyT1 substrate (EC₅₀ = 55 μM). Conclusions Although lidocaine does not function directly on GlyT1, its metabolites MEGX and N-ethylglycine [corrected] were shown to inhibit GlyT1-mediated glycine uptake by at least two different mechanisms. Whereas N-ethylglycine [corrected] was demonstrated to be an alternative GlyT1 substrate, MEGX was shown to inhibit GlyT1 activity in both primary astrocytes and in GlyT1-expressing Xenopuslaevis oocytes at clinically relevant concentrations. These findings provide new insights into the possible mechanisms for the antinociceptive effect of systemic lidocaine.

Abstract We compared fluorescence polarization immunoassay (FPIA, x) and HPLC (y) for measuring monoethylglycinexylidide (MEGX) concentrations in 119 serum samples from 61 liver-transplant donors and recipients. The correlation between the two methods was y = 1.48 micrograms/L + 0.8x (r = 0.89). The bias (mean difference) was 12 micrograms/L (0.055 mumol/L) through the MEGX concentration range measured (0-250 micrograms/L, 0-1.136 mumol/L). We observed a major difference between the two methods in samples from four recipients and one donor. Cross-reactivity in FPIA with lignocaine and two of its metabolites (glycinexylidide and 2,6-xylidine) was < 3%. Samples with high bilirubin concentrations (> 200 mumol/L) required dilution before assay of MEGX by FPIA. Although there was an increase in apparent MEGX concentrations in some samples with increased bilirubin concentrations, the relationship was not constant. Increased plasma concentrations of cholesterol and triglyceride resulted in relatively small increases in apparent MEGX concentrations.

Lidocaine continuous-rate infusions (CRI) are the most commonly used prokinetic in equine practice for the treatment of post-operative ileus and are also increasingly being used in pain management, such as in cases of severe laminitis, and are often used for prolonged durations. To date only limited time/concentration relationships of lidocaine administered as a short term (24hours) CRI to horses are reported. This study examined the time/concentration profile of lidocaine and its active metabolites (GX, MEGX) during a 96 hour lidocaine infusion in eight mature healthy horses. Serum lidocaine concentrations reached steady state by three hours and did not accumulate thereafter. The serum concentration of lidocaine was above the target therapeutic concentration (980ng/ml) only at 6 and 48 hours. The serum lidocaine concentration did not reach the range described as potentially causing toxicity (>1850ng/ml). The MEGX metabolite did not accumulate over time, while the GX metabolite accumulated significantly up to 48 hours and then remained constant. The serum concentrations of lidocaine, MEGX and GX were below the limit of detection within 24 hours of discontinuation of the infusion. None of the horses developed any signs of lidocaine toxicity during the study. It was concluded that the metabolism of lidocaine was not significantly impaired by prolonged infusion, contrasting with studies in dogs and humans. No adverse effects were observed in this study, which with the lack of lidocaine accumulation suggests that prolonged infusions are safe. However the accumulation of GX, a potentially toxic active metabolite, is cause for concern.
Master of Science