Futhan is a serine protease inhibitor and medicine in the treatment of disseminated intravascular coagulation (DIC) and acute pancreatitis. It is metabolized quickly in vivo. Here we show that Futhan reversibly inhibits NMDA receptors in hippocampal neurons and GABAA receptors both in hippocampal neurons and in A549 cells, a human alveolar epithelial cell line. The effect of Futhan on GABAA receptors in A549 cells is much more potent than its effect on GABAA receptors in hippocampal neurons (IC50: 0.9 µM v.s. 7.3 µM). Since GABAA receptors are also expressed in various non-neuronal tissues, particularly in airway epithelia and GABA promotes mucus production during asthma, our findings indicate that Futhan may be developed as a novel aerosolized therapeutic to treat asthma through blocking GABAA receptors in the lung. (IJPPP1108002).
Molecular, Cellular and Biomedical Sciences
International journal of physiology, pathophysiology and pharmacology
Chen X, Li M, Xiong ZG, Orser BA, Macdonald JF, Lu WY. An anti-coagulation agent Futhan preferentially targets GABA(A) receptors in lungepithelia: implication in treating asthma. International journal of physiology, pathophysiology and pharmacology. 2011;3(4):249-56. PubMed PMID: 22162781; PubMed Central PMCID: PMC3230258.