Loperamide: Evidence of interaction with μ and δ opioid receptors

Abstract Loperamide was tested on electrically-evoked contractions using a series of “in vitro” isolated preparations, in comparison with morphine, met-enkephalin, β-endorphin, ethylketocyclazocine used as representative agonists of μ, δ, ϵ, κ receptors respectively. The IC 50 of loperamide on myenteric plexus longitudinal muscle of guinea-pig ileum was found to be 1.90·10 −7 M and equal to that of morphine. The IC 50 on mouse vas deferens was found to be 13.02·10 −7 M. In this tissue, loperamide resulted as active as morphine, but 54 times less active than met-enkephalin (IC 50 0.24·10 −7 M). On the rat vas deferens where, as expected, β-endorphin was strong active (IC 50 1.38·10 −7 M), morphine exerted a stimulatory action within the range 10 −5 M−10 −4 M and loperamide was only poorly depressive. The K e value of naloxone, a specific μ receptor antagonist, against loperamide in the guinea pig ileum was 3.83 nM, and in the mouse vas deferens was 82.87 nM indicating that loperamide in the guinea pig ileum acts on μ receptors while in the mouse vas deferens on another opiate receptor.