PMID: 15252266Jul 15, 2004Paper

Dopaminergic properties and experimental anti-parkinsonian effects of IPX750 in rodent models of Parkinson disease

Clinical Neuropharmacology
Chuantao JiangWeidong Le

Abstract

With a view toward improving the neural bioavailability of administered dopaminergic compounds, including dopamine, synthetic efforts have been directed toward enhancing the brain bioavailability of these compounds by accessing cellular sugar transport systems with stereoselective dopaminergic drugs. While synthesis and chemistry of the resultant class of compounds has recently been described in US Patent No. 6,548,484, the associated biologic properties have not previously been reported. One member of this new class, IPX-750, is a pro-drug dopamine-gluconamine designed to retain stereospecificity of binding at: glucose transporters (GLUT 1/GLUT 3 and intestinal Na/glucose co-transporters SGLT1), dopamine transporter (DAT); and, dopaminergic receptors of the D1/D2 families. Designed to be cleavable by tissue amidases, results reported here show that intact IPX-750 pro-drug retains dopaminergic agonist binding and biologic activities both in vitro and in vivo. IPX-750, like dopamine, exhibited predominant D5/D1 binding specificity with lower binding activity at D2. As expected, binding was highly stereo-specific, ie, IPX-760, a benzamide differing in just a hydrogen atom and keto oxygen from IPX-750, bound with 6-fold lower acti...Continue Reading

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Citations

Jan 17, 2014·Expert Review of Neurotherapeutics·Manuela Pilleri, Angelo Antonini
Sep 9, 2011·Natural Product Reports·Richard W GanttJon S Thorson
May 10, 2017·Materials Science & Engineering. C, Materials for Biological Applications·Hanieh MoradianShahab Faghihi

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