In vivo evidence for the selectivity of ICI 154129 for the delta-opioid receptor.
The in vivo selectivity of the novel delta opioid-receptor antagonist N,N-bisallyl-Tyr-Gly-Gly-psi-(CH2S)-Phe-Leu-OH (ICI 154129) was examined in several opioid-selective models. Antagonism at the delta receptor was demonstrated in the striatal head-turn model in the rat. Intrapallidal injection of the relatively selective delta-receptor agonist D-Ala2,D-Leu5-enkephalin (0.5 micrograms) slowed the head-turn time and this effect was completely prevented by prior subcutaneous administration of ICI 154129 (30 mg/kg). The role of delta receptors in two classical test situations was studied using the mixed opioid agonist etorphine and the antagonists naloxone and ICI 154129. The drug ICI 154129 (30 mg/kg, s.c.) failed to prevent the antinociceptive effects and stimulation of locomotor activity produced by etorphine, whereas the relatively selective mu-opioid receptor antagonist, naloxone was effective in both test situations. The possible involvement of delta receptors in morphine-induced dependence was studied by monitoring the abstinence behaviour precipitated in rats given pellets of morphine by either ICI 154129 or naloxone. Naloxone (0.5 mg/kg, i.p.) precipitated a characteristic withdrawal syndrome in conscious rats and, at a much smaller dose (0.02 mg/kg, i.p.), induced shaking behaviour in pentobarbitone-anaesthetised rats. No withdrawal signs were observed in either model after injection of ICI 154129 (30 mg/kg, s.c.), suggesting that the delta receptors are not involved in dependence on morphine.
Priestley
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Turnbull
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Wei
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D000700:Analgesics; D000818:Animals; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005048:Etorphine / Q000494:pharmacology; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009021:Morphine Dependence / Q000503:physiopathology*; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects* / Q000502:physiology; D017465:Receptors, Opioid, delta
D000700:Analgesics; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D005048:Etorphine; D004743:Enkephalin, Leucine; C036405:ICI 154129