JPET Celsis microsomes equal better data

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wu, D.
Right arrow Articles by Pardridge, W. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wu, D.
Right arrow Articles by Pardridge, W. M.

Central nervous system pharmacologic effect in conscious rats after intravenous injection of a biotinylated vasoactive intestinal peptide analog coupled to a blood-brain barrier drug delivery system

D Wu and WM Pardridge

Department of Medicine, UCLA School of Medicine, USA.

Previous studies showed that intracarotid artery perfusion of biotinylated vasoactive intestinal peptide analog (bio-VIPa) coupled to a blood-brain barrier (BBB) drug delivery vector, OX26/avidin, causes an increase in brain blood flow by 65% in N2O-anesthetized rats. OX26 is a murine monoclonal antibody to the rat transferrin receptor and undergoes receptor-mediated transport through the BBB in vivo. The present investigation examined the central nervous system effects of bio-VIPa after conventional i.v. injection to conscious rats. The VIPa was monobiotinylated (bio) with an-XX-noncleavable (amide) linker, and the bio-XX-VIPa conjugated to OX26/streptavidin (SA) maintained affinity for the VIP receptor in radioreceptor assays. Brain uptake of the bio-XX-VIPa coupled to the OX26/SA vector after i.v. injection was at least 10-fold higher than that of the free bio-XX-VIPa, because of both an increased plasma area under the concentration curve and BBB permeability-surface area product. Administration of the free bio-XX- VIPa increased salivary gland blood flow by 350%, but had no effect on brain blood flow. By contrast, bio-XX-VIPa/OX26-SA conjugate at equal doses (20 micrograms/kg) after i.v. injection increased brain blood flow by 60% in conscious rats, but had no effect on salivary gland blood flow. In summary, the use of the BBB peptide drug delivery system targeted the drug to the central nervous system, and optimized the therapeutic index of the VIPa by enhancing cerebral blood flow and by attenuating side effects in peripheral organs such as salivary gland.

Volume 279, Issue 1, pp. 77-83, 10/01/1996
Copyright © 1996 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


Home page
 Pharmacol. Rev.Home page
M. Delgado, D. Pozo, and D. Ganea
The Significance of Vasoactive Intestinal Peptide in Immunomodulation
Pharmacol. Rev., June 1, 2004; 56(2): 249 - 290.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
B.-W. Song, H. V. Vinters, D. Wu, and W. M. Pardridge
Enhanced Neuroprotective Effects of Basic Fibroblast Growth Factor in Regional Brain Ischemia after Conjugation to a Blood-Brain Barrier Delivery Vector
J. Pharmacol. Exp. Ther., May 1, 2002; 301(2): 605 - 610.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. Kurihara and W. M. Pardridge
Imaging Brain Tumors by Targeting Peptide Radiopharmaceuticals through the Blood-Brain Barrier
Cancer Res., December 1, 1999; 59(24): 6159 - 6163.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1996 by the American Society for Pharmacology and Experimental Therapeutics.