Study of enamine derivatives of phenylglycine as adjuvants for the rectal absorption of insulin.

Abstract

Four phenylglycine enamines were synthesized by reacting sodium phenylglycinate and .beta.-diketones, ethyl acetoacetate, diethyl ethoxymethylenemalonate, ethoxyethyl acetoacetate and 3-acetylbutyrolactone [PG-AcBu Na]. An increase in the immunoreactive serum insulin levels and a decrease in the serum glucose levels was observed in rabbits and dogs following the rectal administration of insulin suppositories in the presence of most PG-enamines. PG-AcBu Na failed to promote the rectal absorption of insulin or inulin. The ability of PG-enamines to interact with Ca2+ was closely correlated with their promoting efficacies on the rectal absorption of insulin in terms of the maximum response to glucose levels and on the rectal absorption of inulin in terms of the concentration-time curve value of serum levels. The lack of promoting efficacy of PG-AcBu Na was explained on the basis of its poor ability to interact with Ca2+.