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391.
MI Strakhova CA Cuff AM Manelli TL Carr DG Witte JL Baranowski TA Vortherms TR Miller L Rundell MJ McPherson RM Adair AA Brito BM Bettencourt BB Yao JM Wetter KC Marsh H Liu MD Cowart JD Brioni TA Esbenshade 《British journal of pharmacology》2009,157(1):44-54
Background and purpose:
The histamine H4 receptor is widely expressed in cells of immune origin and has been shown to play a role in a variety of inflammatory processes mediated by histamine. In this report, we describe the in vitro and in vivo anti-inflammatory properties of a potent histamine H4 receptor antagonist, A-940894 (4-piperazin-1-yl-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-ylamine).Experimental approach:
We have analysed the pharmacological profile of A-940894 at mouse native, rat recombinant and human recombinant and native, histamine H4 receptors by radioligand binding, calcium mobilization, mast cell shape change, eosinophil chemotaxis assays and in the mouse model of zymosan-induced peritonitis.Key results:
A-940894 potently binds to both human and rat histamine H4 receptors and exhibits considerably lower affinity for the human histamine H1, H2 or H3 receptors. It potently blocked histamine-evoked calcium mobilization in the fluorometric imaging plate reader assays and inhibited histamine-induced shape change of mouse bone marrow-derived mast cells and chemotaxis of human eosinophils in vitro. In a mouse mast cell-dependent model of zymosan-induced peritonitis, A-940894 significantly blocked neutrophil influx and reduced intraperitoneal prostaglandin D2 levels. Finally, A-940894 has good pharmacokinetic properties, including half-life and oral bioavailability in rats and mice.Conclusions and Implications:
These data suggest that A-940894 is a potent and selective histamine H4 receptor antagonist with pharmacokinetic properties suitable for long-term in vivo testing and could serve as a useful tool for the further characterization of histamine H4 receptor pharmacology. 相似文献392.
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Nirmal Panthee Battu Kumar Shrestha Sidhartha Pradhan Raamesh Koirala Bishow Pokhrel Abhishek Chaurasiya Amita Paudel Rumi KC 《Clinical Case Reports》2022,10(4)
An 18‐month‐old boy weighing 6 kilograms developed complete collapse of left lung following total correction of Tetralogy of Fallot on the next day of extubation. He received extensive chest physiotherapy, along with lung recruitment maneuver by using bubble CPAP, which failed to show any improvement in lung expansion in 2 days. He was then electively intubated on 3rd postoperative day (POD3) for the purpose of suctioning tracheobronchial secretions and maintaining positive airway pressure to open up the left lung. Good results were obtained immediately after intubation, and he was extubated 9 h later. His lung showed complete aeration afterward. He was transferred out of ICU on POD5 and discharged home on POD10. 相似文献