Met-enkephalin

Where it comes from

Made in

Striatum, periaqueductal grey, spinal cord, adrenal medulla and gut nerves

Sent out by

Pain, stress, exercise; destroyed within seconds by enkephalinases

Acts on

• Pain pathways of the spinal cord and brainstem
• Reward circuits
• Gut (motility)
• Immune cells

What it does

• Dampens pain at the spinal cord and brainstem ¹
• Shapes reward and mood in the striatum
• Slows the gut and cuts the fluid secreted into it, which is what racecadotril exploits ²

In medicine

• Racecadotril, an enkephalinase inhibitor that lets the gut’s own enkephalins last, treats acute diarrhoea in Europe and elsewhere; in children it shortens the illness, on evidence the reviewers rate low to moderate ²
• penKid, a stable fragment of proenkephalin released with it, is a marker of kidney filtration used in research in intensive care

Beyond the body’s own use

• Enkephalinase inhibitors that reach the brain have been tested for pain without opioid dependence; one reached phase 2 in painful diabetic neuropathy and missed its mark
• Met-enkephalin is also called opioid growth factor. Infused weekly in an open-label study of 24 people with advanced pancreatic cancer it was reported to prolong survival against historical controls; with no control group of its own the finding remains unconfirmed, and no trial has repeated it ³
• Racecadotril is not approved in the United States, and the peptide itself is destroyed within seconds in blood, so nothing containing it is taken outside medicine ²