Antinociceptive evaluation of 14 beta-(bromoacetamido)-7,8-dihydro- N(cyclopropylmethyl)-normorphinone in mice.
This study evaluated the supraspinal opioid effects of 14 beta-(bromoacetamido)-7,8-dihydro-N(cyclopropylmethyl)-normorphinone+ ++ (N-CPM-H2BAMO) in the mouse acetic acid-induced writhing and tail-flick assays. In the writhing test, N-CPM-H2BAMO produced a time- and dose-dependent antinociception after i.c.v. administration, with a 50% antinociceptive response being obtained with 0.28 (0.19-0.39) nmol when given 10 min before testing. The antinociceptive effect of N-CPM-H2BAMO was antagonized in a dose-dependent manner by the kappa-selective opioid receptor antagonist, nor-binaltorphimine. In the mouse tail-flick assay, N-CPM-H2BAMO failed to produce any antinociception after i.c.v. administration. N-CPM-H2BAMO produced a dose-dependent antagonism of morphine-induced antinociception but not antinociception induced by the delta-opioid receptor agonist [D-Pen2,D-Pen5]enkephalin. Nor-binaltorphimine (0.3 nmol) at dose that completely antagonized N-CPM-H2BAMO-induced antinociception in the writhing assay did not prevent the antagonistic effect of N-CPM-H2BAMO on morphine-induced antinociception. Therefore, these data indicate that N-CPM-H2BAMO produces antinociception by acting at supraspinal kappa-opioid receptors in the writhing assay, and also acts as a mu-opioid receptor antagonist.
Jiang
Q
Q
Department of Pharmacology, University of Rochester, School of Medicine and Dentistry, NY 14642.
Seyed-Mozaffari
A
A
Archer
S
S
Bidlack
J M
JM
D000085:Acetates / Q000633:toxicity; D019342:Acetic Acid; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004347:Drug Interactions; D004091:Hydromorphone / Q000031:analogs & derivatives* / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D010147:Pain Measurement; D017465:Receptors, Opioid, delta / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000187:drug effects* / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism
D000085:Acetates; D000700:Analgesics; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C051843:binaltorphimine; C084455:14-(bromoacetamido)-7,8-dihydro-N-(cyclopropylmethy)normorphinone; D009271:Naltrexone; D019342:Acetic Acid; D004091:Hydromorphone