TY - JOUR
T1 - Time course of antagonism of morphine antinociception by intracerebroventricularly administered naloxone in the rat
AU - Porreca, Frank
AU - Cowan, Alan
AU - Tallarida, Ronald J.
N1 - Funding Information:
This work was supported by Grant DA 02322 from the National Institute on Drug Abuse. We also thank Endo Labs for the gift of naloxone, and Remus Beretta for his technical assistance.
PY - 1981/11/19
Y1 - 1981/11/19
N2 - This kinetic profile and half-life of naloxone were studied for possible use in determination of pA2 and KB in vivo. Rats were given morphine subcutaneously and after 15 min naloxone or saline, intracerebroventricularly. A further 15 min later, and at 15 min intervals up to 135 min after morphine, the animals were tested for analgesia in the tail flick test. The dose-response curves of the naloxone group were shifted to the right of those for the saline group. Theamount of displacement decreased with time, indicative of the disappearance of naloxone. The graph of log (dose ratio-1) vs. time was linear with negative slope, in agreement with the time-dependent form of the equation for competitive antagonism. From this slope, the half-life of naloxone was calculated to be 13.3 min. These results demonstrate that the time-dependent method is useful in obtaining the kinetics of centrally acting opiate antagonists.
AB - This kinetic profile and half-life of naloxone were studied for possible use in determination of pA2 and KB in vivo. Rats were given morphine subcutaneously and after 15 min naloxone or saline, intracerebroventricularly. A further 15 min later, and at 15 min intervals up to 135 min after morphine, the animals were tested for analgesia in the tail flick test. The dose-response curves of the naloxone group were shifted to the right of those for the saline group. Theamount of displacement decreased with time, indicative of the disappearance of naloxone. The graph of log (dose ratio-1) vs. time was linear with negative slope, in agreement with the time-dependent form of the equation for competitive antagonism. From this slope, the half-life of naloxone was calculated to be 13.3 min. These results demonstrate that the time-dependent method is useful in obtaining the kinetics of centrally acting opiate antagonists.
KW - Half-life
KW - Intracerebroventricular administration
KW - Morphine
KW - Naloxone
KW - Pharmacokinetics
KW - Time-dependent method
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U2 - 10.1016/0014-2999(81)90008-X
DO - 10.1016/0014-2999(81)90008-X
M3 - Article
C2 - 7318922
AN - SCOPUS:0019814631
SN - 0014-2999
VL - 76
SP - 55
EP - 59
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1
ER -