The effect of naltrindole on spinal and supraspinal delta opioid receptors and analgesia.
The relationship between changes in binding for delta 1 (DPDPE) and delta 2 (DSLET) selective ligands were compared to potency changes for these ligands following naltrindole (NTI) in mice. Mice were injected s.c. with NTI (1 or 20 mg/kg) or saline and 1 hr later sacrificed for binding studies ([3H]DSLET, [3H]DPDPE) using whole brain or spinal cord. Other mice were injected s.c. with NTI (1 or 20 mg/kg) or saline and then injected IT or ICV with DSLET or DPDPE and were tested for analgesia using the tailflick test. In saturation binding studies, NTI decreased specific binding of [3H]DPDPE and [3H]DSLET in brain and spinal cord, but had no selective effect on either ligand. In contrast, in functional studies, NTI decreased analgesic potency of spinally and supraspinally administered DSLET more than DPDPE. Thus in functional studies NTI produced a selective effect on the delta 2 agonist DSLET; but in binding studies, NTI had no selective effect on the binding of [3H]DSLET and [3H]DPDPE.
Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St. John's University, Queens, NY 11439.
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D000698:Analgesia; D000700:Analgesics / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D020881:Enkephalin, D-Penicillamine (2,5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D004745:Enkephalins / Q000378:metabolism / Q000494:pharmacology; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D007700:Kinetics; D008297:Male; D051379:Mice; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D017465:Receptors, Opioid, delta / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure
D000700:Analgesics; D004745:Enkephalins; D017465:Receptors, Opioid, delta; D004743:Enkephalin, Leucine; D009271:Naltrexone; C034318:enkephalin, Ser(2), Leu(5), Thr(6)-; D020881:Enkephalin, D-Penicillamine (2,5)-; C055382:naltrindole