Document Report Card
Basic Information
ID: ALA5029183
Journal: J Med Chem
Title: Novel Cyclic Endomorphin Analogues with Multiple Modifications and Oligoarginine Vector Exhibit Potent Antinociception with Reduced Opioid-like Side Effects.
Authors: Zhang YZ, Wang MM, Wang SY, Wang XF, Yang WJ, Zhao YN, Han FT, Zhang Y, Gu N, Wang CL.
Abstract: Endomorphins (EMs) are potent pharmaceuticals for the treatment of pain. Herein, we investigated several novel EM analogues with multiple modifications and oligoarginine conjugation. Our results showed that analogues 1-6 behaved as potent μ-opioid agonists and enhanced stability and lipophilicity. Analogues 5 and 6 administered centrally and peripherally induced significant and prolonged antinociceptive effects in acute pain. Both analogues also produced long-acting antiallodynic effects against neuropathic and inflammatory pain. Furthermore, they showed a reduced acute antinociceptive tolerance. Analogue 6 decreased the extent of chronic antinociceptive tolerance, and analogue 5 exhibited no tolerance at the supraspinal level. Particularly, they displayed nontolerance-forming antinociception at the peripheral level. In addition, analogues 5 and 6 exhibited reduced or no opioid-like side effects on gastrointestinal transit, conditioned place preference (CPP), and motor impairment. The present investigation established that multiple modifications and oligoarginine-vector conjugation of EMs would be helpful in developing novel analgesics with fewer side effects.
CiteXplore: 34781680