In vivo disposition and metabolism of enkephalins: relationship to analgesic properties.

After intravenous injection, both Met5-enkephalin and D-Ala2-Met5-enkephalinamide rapidly entered the brains of mice. Both peptides obtained similar concentrations. The t-1/2 for D-Ala2-Met5-enkephalinamide in the brain (0.7 minutes) corresponds roughly to its analgesic t-1/2 (1.7 minutes); thus, rapid metabolism appears to account for the short duration of analgesia seen with this compound. Met5-enkephalin, on the other hand, although attaining similar brain concentrations, failed to elicit analgesia. Rapid metabolism alone does not account for this lack of analgesic effect.