Novel chimeric peptides based on endomorphins and ghrelin receptor antagonist produced supraspinal antinociceptive effects with reduced acute tolerance in mice.

In vivo study in mice

“Upon intracerebroventricular (i.c.v.) administration in mice, both EM-1-DLS and EM-2-DLS exhibited dose- and time-dependent antinociceptive effects in the tail withdrawal test.”

Mice

“Upon intracerebroventricular (i.c.v.) administration in mice, both EM-1-DLS and EM-2-DLS exhibited dose- and time-dependent antinociceptive effects in the tail withdrawal test.”

Chimeric peptides acted as kappa-opioid receptor preferring agonists with weak mu-opioid and ghrelin receptor agonist activity.

“Functional assays demonstrated that EM-1-DLS and EM-2-DLS acted as κ-opioid receptor (κ-OR)-preferring agonists, weak μ-opioid receptors (μ-OR) and ghrelin receptor (GHSR) agonists.”

EM-1-DLS showed higher antinociceptive potency than EM-1.

“EM-1-DLS demonstrated the highest antinociceptive potency among the peptides, with an ED50 approximately 8-fold greater than EM-1, while EM-2-DLS showed comparable effects to EM-2.”

EM-1-DLS induced significantly lower acute tolerance compared to EM-1.

“Additionally, acute antinociceptive tolerance was investigated, revealing that EM-1-DLS induced a tolerance ratio of 2.33-fold, significantly lower than the 5.19-fold ratio induced by EM-1.”