AIMTo determine whether cysteinyl leukotriene receptor 1 (CysLT1 receptor) is involved in N-methyl-D-aspartate (NMDA)-induced excitotoxic injury in the mouse brain.METHODSBrain injury was induced by NMDA microinjection (50-150 nmol in 0.5 microL) into the cerebral cortex. The changes in CysLT1 receptor expression 24 h after NMDA injection and the effects of a CysLT1 receptor antagonist, pranlukast (0.01 and 0.1 mg/kg), an NMDA receptor antagonist, ketamine (30 mg/kg), and an antioxidant, edaravone (9 mg/kg) were observed.RESULTSIn the NMDA-injured brain, the CysLT1 receptor mRNA, and protein expression were upregulated, and the receptor was mainly localized in the neurons and not in the astrocytes. Pranlukast, ketamine and edaravone decreased NMDA-induced injury; pranlukast (0.1 mg/kg) and ketamine inhibited the upregulated expression of the CysLT1 receptor.CONCLUSIONCysLT1 receptor expression in neurons is upregulated after NMDA injection, and NMDA-induced responses are inhibited by CysLT1 receptor antagonists, indicating that the increased CysLT1 receptor is involved in NMDA excitotoxicity.

Clinical Pharmacology in Drug Development

Pharmacokinetics and Bioequivalence of Two Formulations of Montelukast Sodium Tablets in Healthy Chinese Volunteers Under Fasting and Fed Conditions

Article

作者: Huang, Zhaoming ; Wu, Xinghong ; Hu, Jiawei ; Rao, Xiali

AbstractMontelukast sodium is a leukotriene type 1 receptor antagonist that can be used for the prophylaxis and treatment of asthma. However, the pharmacokinetics of montelukast sodium tablets (10 mg) remain unclear in healthy Chinese subjects. Here, a single‐dose randomized, open‐label, 2‐sequence, and 2‐period crossover (7‐day washout period between treatments) study was performed to compare the pharmacokinetics and bioequivalence between the test products and the reference at a single dose of 10 mg among healthy Chinese subjects under fasting and fed conditions. Blood samples were collected at specified time points to analyze the plasma concentrations of montelukast by a validated liquid chromatography‐tandem mass spectrometry method. The results showed that the 90% confidence interval values of the geometric mean ratio of test/reference for the maximum plasma drug concentration, area under the concentration‐time curve from time 0 to the end, and area under the concentration‐time curve from time 0 to infinity were within the range of 80%‐125%. Moreover, both the test and reference formulations were safe and well tolerated, with no occurrence of severe adverse events. These results demonstrate that both the test montelukast sodium tablets and the reference showed similar bioequivalence, safety, and tolerability among healthy Chinese subjects under fasting and fed conditions.

100 项与 CysLT 1 receptor antagonist(University College Dublin) 相关的药物交易

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