[2] Met-enkephalin was discovered and characterized by John Hughes, Hans Kosterlitz, et al. in 1975 after a search for endogenous ligands of the opioid receptors.
[citation needed] Met-enkephalin is found mainly in the adrenal medulla and throughout the central nervous system (CNS), including in the striatum, cerebral cortex, olfactory tubercle, hippocampus, septum, thalamus, and periaqueductal gray, as well as the dorsal horn of the spinal cord.
[2] It is also present in the periphery, notably in some primary afferent fibers that innervate the pelvic viscera.
[4] In addition, anabolism of proenkephalin A results in the production of one copy each of two C-terminal-extended met-enkephalin derivatives, the heptapeptide met-enkephalin-arg-phe (261–267), and the octapeptide met-enkephalin-arg-gly-leu (186–193),[4] though whether they affect the opioid receptors in a similar manner as met-enkephalin is not entirely clear.
[3][11] These properties are considered undesirable in pharmaceuticals as large doses would need to be administered multiple times an hour to maintain a therapeutically relevant effect, making it unlikely that met-enkephalin will ever be used as a medicine.