metkephamid and Morphine-Dependence

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analogs FK 33-824 and metkephamid were determined after systemic and intracerebroventricular (i.c.v.) administration in withdrawn morphine-dependent rhesus monkeys.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.

Topics: Animals; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Enkephalin, Methionine; Hormones; Humans; Injections, Intraventricular; Injections, Subcutaneous; Macaca mulatta; Morphine; Morphine Dependence