CLOCINNAMOX DOSE-DEPENDENTLY ANTAGONIZES MORPHINE-ANALGESIA AND [H-3]DAMGO BINDING IN RATS

Citation
Ca. Paronis et Jh. Woods, CLOCINNAMOX DOSE-DEPENDENTLY ANTAGONIZES MORPHINE-ANALGESIA AND [H-3]DAMGO BINDING IN RATS, European journal of pharmacology, 337(1), 1997, pp. 27-34
Citations number
28
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
00142999
Volume
337
Issue
1
Year of publication
1997
Pages
27 - 34
Database
ISI
SICI code
0014-2999(1997)337:1<27:CDAMA[>2.0.ZU;2-C
Abstract
Clocinnamox is a long-lasting, nonequilibrium, mu-opioid receptor anta gonist in mice and monkeys. The present studies examined the in vive a nd ex vivo effects of clocinnamox in rats. Under control conditions, m orphine dose-dependently increased tail-withdrawal latencies from 50 d egrees C water, with a mean ED50 of 7.3 +/- 1.1 mg/kg. Clocinnamox ant agonized the antinociceptive effects of morphine. 1.0 mg/kg clocinnamo x displaced the morphine dose-response curve 4-fold to the right of th e control curve and 10 mg/kg clocinnamox eliminated morphine's antinoc iceptive effects at doses up to 1000 mg/kg for at least seven days. Th ere was a gradual recovery of the antinociceptive response to morphine ; however, the morphine dose-response curve did not return to its orig inal position by five weeks after 10 mg/kg clocinnamox. Whole brain me mbranes were prepared from separate groups of rats for determination o f binding parameters of [H-3][D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephal in (DAMGO). Clscinnamox dose-dependently decreased [H-3]DAMGO binding ex vivo and the decreased binding was a result of changes in B-max. Th e control B-max for [H-3]DAMGO was 234 +/- 8 fmol/mg protein; in membr anes prepared from the rats pretreated with 10 mg/kg clocinnamox, the B-max value for [H-3]DAMGO was 54 +/- fmol/mg protein. The B-max value s for [3H]DAMGO binding after an injection of 10 mg/kg clocinnamox ret urned towards control values gradually, four after clocinnamox the B-m ax was 178 +/- 10 fmol/mg protein. These results suggest that clocinna mox is a long-lasting, mat nonequilibrium mu-opioid receptor antagonis t in rats. (C) 1097 Elsevier Science B.V.