Rapid high-affinity transport of a chemotherapeutic amino acid across the blood-brain barrier.
作者： David T. Vistica , Nigel H. Greig , Stanley I. Rapoport , David Purdon , Yoshiaki Takada
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摘要: The therapeutic efficacy of many anticancer drugs against intracerebral tumors is limited by poor uptake into the central nervous system. One way to enhance brain delivery design agents that are transported saturable nutrient carriers blood-brain barrier. In this paper, we describe a nitrogen mustard amino acid, dl-2-amino-7-bis[(2-chloroethyl)amino]-1,2,3,4-tetrahydro-2-naphthoic taken up with high affinity large neutral acid carrier Brain transport in rat was found be rapid (cerebrovascular permeability-surface area product ∼2 × 10−2 ml/s/g), and inhibitable acids. Maximal influx rate (Vmax) half-saturation ( Km ) constants equaled 0.26 nmol/min/g 0.19 µm, respectively, parietal cortex. Regional exceeded clinical analogue, melphalan, >20-fold. results demonstrate drug modification produce high-affinity ligands for cerebrovascular viable means treatment other system disorders.
aacrjournals.org 参考文章(30)
Quentin R. Smith, Quantitation of Blood-Brain Barrier Permeability Implications of the Blood-Brain Barrier and Its Manipulation. pp. 85- 118 ,(1989) , 10.1007/978-1-4613-0701-3_4
Jeffrey A. Stephenson, Jonathon L. Finlay, Pathophysiologic Basis for Brain Tumor Chemotherapy Springer, Boston, MA. pp. 233- 271 ,(1990) , 10.1007/978-1-4613-1501-8_8
A.B. Mauger, W.C.J. Ross, Aryl-2-halogenoalkylamines—XX Biochemical Pharmacology. ,vol. 11, pp. 847- 858 ,(1962) , 10.1016/0006-2952(62)90180-6
H N Christensen, M E Handlogten, I Lam, H S Tager, R Zand, A Bicyclic Amino Acid to Improve Discriminations among Transport Systems Journal of Biological Chemistry. ,vol. 244, pp. 1510- 1520 ,(1969) , 10.1016/S0021-9258(18)91789-8
William M. Pardridge, Eain M. Cornford, Graeme J. Finlay, William R. Wilson, James W. Paxton, Deborah Young, Melphalan Penetration of the Blood-Brain Barrier via the Neutral Amino Acid Transporter in Tumor-bearing Brain Cancer Research. ,vol. 52, pp. 138- 143 ,(1992)
Philip S. Schein, Dianna Green, Eugene McPherson, Stephen W. Dean, 6-[Bis(2-chloroethyl)amino]-6-deoxygalactopyranose Hydrochloride (C6-Galactose Mustard), a New Alkylating Agent with Reduced Bone Marrow Toxicity Cancer Research. ,vol. 47, pp. 696- 699 ,(1987)
Hing-Yat Peter Lam, Marjorie Lee, Asher Begleiter, Gerald J. Goldenberg, Evidence for Carrier-mediated Transport of Melphalan by L5178Y Lymphoblasts in Vitro Cancer Research. ,vol. 37, pp. 755- 760 ,(1977)
E A Neuwelt, D L Goldman, S A Dahlborg, J Crossen, F Ramsey, S Roman-Goldstein, R Braziel, B Dana, Primary CNS lymphoma treated with osmotic blood-brain barrier disruption: prolonged survival and preservation of cognitive function. Journal of Clinical Oncology. ,vol. 9, pp. 1580- 1590 ,(1991) , 10.1200/JCO.1991.9.9.1580
Quentin R. Smith, Yoshio Takasato, Daniel J. Sweeney, Stanley I. Rapoport, Regional cerebrovascular transport of leucine as measured by the in situ brain perfusion technique Journal of Cerebral Blood Flow and Metabolism. ,vol. 5, pp. 300- 311 ,(1985) , 10.1038/JCBFM.1985.39
Stanley I. Rapoport, Blood-brain barrier Nature. ,vol. 283, pp. 414- 414 ,(1980) , 10.1038/283414A0