Thursday, September 27, 2012
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Activation of sphingosine
1-phosphate receptor to improve drug delivery across the
blood brain barrier (BBB)
receptor agonists could help improve drug delivery across the BBB. In rat
brains, sphingosine 1-phosphate receptor agonists increased BBB penetration
of the opioid
receptor agonist loperamide and the chemotherapeutic paclitaxel
compared with delivering the two compounds without a sphingosine 1-phosphate
receptor agonist. In the rat model, the sphingosine 1-phosphate receptor
agonists decreased P
drug efflux compared with no agonist. Next steps include studies to elucidate
the mechanism by which sphingosine 1-phosphate receptor agonists modulate
P-gp-mediated drug efflux.
Tanabe Pharma Corp. and Novartis
AG market the sphingosine 1-phosphate receptor agonist Gilenya
to treat relapsing forms of multiple sclerosis (MS).
At least eight other companies have sphingosine 1-phosphate receptor-targeting
compounds in Phase II testing or earlier to treat various diseases.
Loperamide is a generic drug for diarrhea.
Published online Sept. 27, 2012
status not applicable
Cannon, R.E. et al.
Proc. Natl. Acad. Sci. USA; published online Sept. 4, 2012;
Contact: Ronald E. Cannon, National Institute of
Environmental Health Sciences, National Institutes of Health, Research
Triangle Park, N.C.
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