Antinociception after intracerebroventricular administration of naltrindole in the mouse.
Intracerebroventricular (i.c.v.) injection of the delta-opioid receptor antagonist naltrindole hydrochloride (2.2-22.2 nmol) in mice produced a dose-dependent increase in tail flick and hot plate latencies with respective ED50 and 95% confidence limits of 10.6 (8.3-13.9) and 16.4 (9.2-62.3) nmol. This increase in response latencies was antagonized by 1 mg/kg s.c. naloxone or by i.c.v. coadministration of 1.4 nmol ICI-174,864, a selective peptidergic delta-receptor antagonist. Pretreatment 24 h earlier with the irreversible mu-receptor antagonist beta-funaltrexamine (6 nmol i.c.v.) or 1 h earlier with the selective kappa-receptor antagonist nor-binaltorphimine (100 nmol i.c.v.) did not attenuate the antinociceptive effects of naltrindole. These data indicate that high doses of naltrindole may have agonist activity at supraspinal delta-opioid receptors in the mouse.
Stapelfeld
A
A
Neurological Diseases Research, G.D. Searle & Co., Chicago, IL 60077.
Hammond
D L
DL
Rafferty
M F
MF
D000818:Animals; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000008:administration & dosage*; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009019:Morphinans / Q000008:administration & dosage*; D009271:Naltrexone / Q000031:analogs & derivatives*; D009292:Narcotic Antagonists / Q000008:administration & dosage; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology; D017465:Receptors, Opioid, delta
D007211:Indoles; D009019:Morphinans; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D009271:Naltrexone; C055382:naltrindole