| TCP-FA4: a derivative of tranylcypromine showing improved blood-brain permeability. | |
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MedLine Citation:
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PMID: 19679106 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A variety of approaches have been taken to improve the brain penetration of pharmaceutical agents. The amphipathic character of a compound can improve its interaction with the lipid bilayer within cell membranes, and as a result improve permeability. Fatty acid chains or lipoamino acids of various lengths were attached to tranylcypromine (TCP), in an attempt to improve the blood-brain barrier (BBB) permeability by increasing the lipophilicity as well as the amphiphatic character of the drug. TCP-FA4, one of the derivatives containing a four carbon alkyl acid chain, showed the greatest improvement in permeability. This molecule was slightly neuroprotective in a beta-amyloid-induced neurodegeneration assay and may also be capable of upregulating brain derived neurotrophic factor (BDNF), as indicated by cell culture assays using human umbilical vein endothelial cells. Since decreased levels of BDNF are observed in many CNS disorders, and direct injection of BDNF is not a viable option due to its poor permeability across the BBB, small molecules capable of regulating BDNF that also cross the BBB may be an interesting treatment option. |
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Authors:
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Kelly E Desino; Rosario Pignatello; Salvatore Guccione; Livia Basile; Sabah Ansar; Mary Lou Michaelis; Rona R Ramsay; Kenneth L Audus |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-08-11 |
Journal Detail:
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Title: Biochemical pharmacology Volume: 78 ISSN: 1873-2968 ISO Abbreviation: Biochem. Pharmacol. Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-10-12 Completed Date: 2009-10-26 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0101032 Medline TA: Biochem Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 1412-7 Citation Subset: IM |
Affiliation:
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The University of Kansas, Department of Pharmaceutical Chemistry, 2095 Constant Ave, Lawrence, KS 66047, USA. Kelly.Desino@abbott.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amyloid beta-Protein
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pharmacology Animals Blood-Brain Barrier / cytology, metabolism* Brain / blood supply Brain-Derived Neurotrophic Factor / biosynthesis Cattle Cell Survival / drug effects Cells, Cultured Endothelial Cells / drug effects, metabolism Endothelium, Vascular / cytology Humans Microvessels / cytology Monoamine Oxidase Inhibitors / pharmacokinetics, pharmacology Neurons / cytology, drug effects Neuroprotective Agents / pharmacokinetics*, pharmacology Peptide Fragments / pharmacology Permeability Rats Rats, Sprague-Dawley Tranylcypromine / analogs & derivatives*, pharmacokinetics*, pharmacology Umbilical Veins / cytology Up-Regulation |
| Chemical | |
Reg. No./Substance:
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0/Amyloid beta-Protein; 0/Brain-Derived Neurotrophic Factor; 0/Monoamine Oxidase Inhibitors; 0/Neuroprotective Agents; 0/Peptide Fragments; 0/amyloid beta-protein (25-35); 0/tranylcypromine-FA4; 155-09-9/Tranylcypromine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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