Selective delta-opioid receptor antagonism by ICI 174,864 in the central nervous system |
| |
Authors: | A Dray L Nunan |
| |
Institution: | University of Arizona, Department of Pharmacology, Health Sciences Center College of Medicine, Tucson, AZ 85724, USA |
| |
Abstract: | The effects of the novel gamma-opioid receptor antagonist ICI 174,864 (N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH: Aib = alpha-aminoisobutyric acid) have been examined in the CNS in vivo using spontaneous reflex contractions of the rat urinary bladder as an index of activity. Bladder contractions were inhibited by equipotent intracerebroventricular (ICV) doses of the selective mu-agonist DAGO D-Ala2, MePhe4,Gly-(ol)5]enkephalin and the delta-agonist DPDPED-Pen2, D-Pen5]enkephalin. ICI 174,864 (1-3 micrograms) administered by the same route produce a selective and reversible antagonism of DPDPE effects. At higher doses (6-15 micrograms, ICV) ICI 174,864 exhibited marked agonistic activity, producing inhibition of bladder contractions that were resistant to ICV naloxone (1-2 micrograms). Thus ICI 174,864 was considered a selective central delta-opioid receptor antagonist but its usefulness was limited by additional agonistic properties. |
| |
Keywords: | ICI 174 864 δ-Opioid antagonism Central activity |
本文献已被 ScienceDirect 等数据库收录! |
|