The effects of the degradation-resistant enkephalin analogs FK 33-824 and metkephamid were determined after systemic and intracerebroventricular (i.c.v.) administration in withdrawn morphine-dependent rhesus monkeys. Both peptides suppressed completely signs of 12-hr morphine deprivation, as does the prototype mu-receptor agonist morphine. The peptides were 100 and 2000 times more potent, respectively, after i.c.v. than s.c. injection. Thus, although peptidase-resistant, these compounds have restricted entrance into the central nervous system after systemic administration. The i.c.v. administration of compounds in rhesus monkeys should prove to be a valuable tool in the study of peptide ligands for opiate receptors.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)