NASAL MUCOSAL METABOLISM AND ABSORPTION OF PENTAPEPTIDE ENKEPHALIN ANALOGS HAVING VARYING N-TERMINAL AMINO-ACIDS

A series of enkephalin analogs with varying amino acids on the N-termi nus were synthesized and evaluated in rats in situ for their hydrolyti c stability and absorption when administered nasally. The amino acids on the N-terminus were tyrosine (Y), alanine (A), serine (S), lysine ( K), and aspartic acid (D). These amino acids represent different charg es and sizes. Among these peptides, only the peptide carrying aspartic acid on the N-terminus was stable. The rank order of degradation rate s was YGGFL > AGGFL > SGGFL, KGGFL > DGGFL. These results suggest that there are relatively high activities of aminopeptidases N and B and r elatively low activity of aminopeptidase A in the rat nasal mucosa. Ab sorption studies were performed to determine the absorption rate of DG GFL, by measuring percentage recovery of nasal doses vs time. After a 50 mu L dose of a 3 mg/mL solution, this peptide exhibited an absorpti on half-life of 21 min, which is similar to the nasal absorption rate of YGGFL.