TY - JOUR
T1 - Receptor binding and analgesic properties of oxymorphazone
AU - Galetta, Steven
AU - Ling, Geoffrey S.F.
AU - Wolfin, Louis
AU - Pasternak, Gavril W.
N1 - Funding Information:
We thank Drs. Posner and Ahern for their aid and M. Buatti and S. Nishimura for technical assistance. These studies were supported in part by grants from NIDA (DA 02615). GWP is supported by NINCDS Teacher-Investigator Award I-KO7NS415 and GSFL by Fellowship DRG-564 of the Damon Runyon-Walter Winchell Cancer Fund.
PY - 1982/9
Y1 - 1982/9
N2 - The 14-hydroxydihydromorphinone hydrazones have been quite useful in studying aspects of opiate receptor binding and function. The most extensively studied, naloxazone, effectively and selectively inhibits high affinity (mu1) sites in vitro and morphine analgesia in vivo. We now report on the actions of oxymorphazone on receptor binding in vitro and on analgesia in vivo. Oxymorphazone effectively lowers 3H-opioid binding despite extensive washes with the same selectively for high affinity, or mu1, binding sites as naloxazone. Acutely, oxymorphazone was less potent in vivo than oxymorphone (ED50's of 0.8 and 0.4 mg/kg, respectively). Both quantal dose response curves were parallel. At higher doses (100 mg/kg), 83% of animals given oxymorphazone over 20 hr previously were analgesic whereas none of the oxymorphone animals were (p<0.001). Oxymorphazone also produced prolonged analgesia after icv administration. These results, in addition to other studies, suggest that oxymorphazone's actions cannot be adequately explained by pharmacokinetic differences from oxymorphone and supports the hypothesis that the drug works via prolonged receptor binding.
AB - The 14-hydroxydihydromorphinone hydrazones have been quite useful in studying aspects of opiate receptor binding and function. The most extensively studied, naloxazone, effectively and selectively inhibits high affinity (mu1) sites in vitro and morphine analgesia in vivo. We now report on the actions of oxymorphazone on receptor binding in vitro and on analgesia in vivo. Oxymorphazone effectively lowers 3H-opioid binding despite extensive washes with the same selectively for high affinity, or mu1, binding sites as naloxazone. Acutely, oxymorphazone was less potent in vivo than oxymorphone (ED50's of 0.8 and 0.4 mg/kg, respectively). Both quantal dose response curves were parallel. At higher doses (100 mg/kg), 83% of animals given oxymorphazone over 20 hr previously were analgesic whereas none of the oxymorphone animals were (p<0.001). Oxymorphazone also produced prolonged analgesia after icv administration. These results, in addition to other studies, suggest that oxymorphazone's actions cannot be adequately explained by pharmacokinetic differences from oxymorphone and supports the hypothesis that the drug works via prolonged receptor binding.
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U2 - 10.1016/0024-3205(82)90388-5
DO - 10.1016/0024-3205(82)90388-5
M3 - Article
C2 - 6183551
AN - SCOPUS:0020355857
SN - 0024-3205
VL - 31
SP - 1389
EP - 1392
JO - Life Sciences
JF - Life Sciences
IS - 12-13
ER -