ヒグチ　ケイ   Higuchi Kei   樋口　慧    所属   東邦大学  薬学部 薬学科    職種   准教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Transport characteristics of tramadol in the blood-brain barrier.
掲載誌名	正式名：Journal of pharmaceutical sciences ISSNコード：0022-3549/1520-6017
掲載区分	国外
出版社	WILEY-BLACKWELL
巻・号・頁	103(10),pp.3335-41
著者・共著者	Atsushi Kitamura,Kei Higuchi,Takashi Okura,Yoshiharu Deguchi
担当区分	2nd著者
発行年月	2014/10
概要	Tramadol is a centrally acting analgesic whose action is mediated by both agonistic activity at opioid receptors and inhibitory activity on neuronal reuptake of monoamines. The purpose of this study was to characterize the blood-brain barrier (BBB) transport of tramadol by means of microdialysis studies in rat brain and in vitro studies with human immortalized brain capillary endothelial cells (hCMEC/D3). The Kp,uu,brain value of tramadol determined by rat brain microdialysis was greater than unity, indicating that tramadol is actively taken up into the brain across the BBB. Tramadol was transported into hCMEC/D3 cells in a concentration-dependent manner. The uptake was inhibited by type II cations (pyrilamine, verapamil, etc.), but not by substrates of organic cation transporter OCTs or OCTN2. It was also inhibited by a metabolic inhibitor but was independent of extracellular sodium or membrane potential. The uptake was altered by changes of extracellular pH, and by ammonium chloride-induced intracellular acidification, suggesting that transport of tramadol is driven by an oppositely directed proton gradient. Thus, our in vitro and in vivo results suggest that tramadol is actively transported, at least in part, from blood to the brain across the BBB by proton-coupled organic cation antiporter.
DOI	10.1002/jps.24129
PMID	25175482