Pharmacology of a gut motility stimulating enkephalin analogue

The enkephalin analogue pentapeptide Hoe 825 (Tyr-D-Lys-Gly-Phe-L-homocysteine-thiolactone) is a mixed μ/δ opiate agonist. The peptide stimulated interdigestive gut motility at all parts of the intestine in conscious and anaesthetized animals. In dogs digestive motility, measuring mechanical activity, was stimulated with respect to segmental and propulsive properties. The canine uterus was sensitive to the enkephalin. Hoe 825 acts by i.v. or s.c. application, whereas the latter increases the duration of action significantly. The compound's effect can be blocked by naloxone indicating a receptor mediated action, which is localised peripherally. The compound is devoid of a dependence risk, because it does not penetrate into the CNS. At therapeutic doses (in the dog 0.5-2 μg/kg i.v.) the compound does not affect cardiovascular, renal or endocrine functions and was without effect on serum blood glucose levels in rats and rabbits.