DRUG DELIVERY APPROACH TO PREVENT THE ACCUMULATION OF THE EXCITATORY AMINO ACID RECEPTOR ANTAGONIST IN THE KIDNEY

Abstract

We demonstrated that S-1080, a dual antagonist for the NMDA receptor glycine site and the AMPA receptor, was excreted by the kidney by the anion transport system. The accumulation of 51080 in the kidney was observed after intravenous administration of more than 25 mg/kg of S-1080 in rats. This renal accumulation of S-1080 was clearly diminished by the co-administration of N-benzoyl-β-alanine. We studied the mechanism that N-benzoyl-β-alanine ameliorates S-1080 accumulation in the kidney and found that N-benzoyl-β-alanine, which is rapidly excreted by the kidney, increases S-1080 solubility in urine.