THE ENZYMATIC DEGRADATION AND TRANSPORT OF LEUCINE-ENKEPHALIN AND 4-IMIDAZOLIDINONE ENKEPHALIN PRODRUGS AT THE BLOOD-BRAIN-BARRIER

In this study, the stability in and transport across a cell culture mo del of the blood-brain barrier (BBB) is investigated for leucine-enkep halin (Leu-enkephalin) and four 4-imidazolidinone prodrugs of Leu-enke phalin. The results show that Leu-enkephalin is degraded in the cell c ulture model of the BBB both by cytosolic and plasma membrane bound en zymes. It is likely that aminopeptidase is the predominant enzyme resp onsible for the degradation of Leu-enkephalin. All four 4-imidazolidin one prodrugs of Leu-enkephalin examined showed an increased stability of Leu-enkephalin against degradation by both plasma membrane bound an d cytosolic enzymes. Consequently, the transport properties of Leu-enk ephalin is also improved by up to 60% by formation of 4-imidazolidinon e prodrugs. (C) 1998 Elsvier Science B.V. All rights reserved.