Estimation of the dissociation constant of naloxone in the naive and morphine-tolerant guinea-pig isolated ileum: analysis by the constrained Schild plot.
The pA2 values for naloxone-morphine were determined using ilea taken from naive and morphine-tolerant guinea-pigs. This constant decreased from 8.56 (+/- 0.22) in the naive to 7.95 (+/- 0.12) in tolerant tissues. The values of the pA2's were based on Schild plots using conventional regression techniques; this regression resulted in values of -log KB of 8.79 (+/- 1.5) and 8.18 (+/- 1.2) in naive and morphine-tolerant ilea, respectively. While pA2 differed, the difference in -log KB was not statistically significant. Since these two values are theoretically equivalent, the above finding appears paradoxical. Constraining the slope of the Schild plot to the theoretically required -1 resolved this discrepancy by reducing the error inherent in the calculation of -log KB determined by conventional regression.
D000818:Animals; D004361:Drug Tolerance; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000378:metabolism*; D013223:Statistics as Topic
D009270:Naloxone; D009020:Morphine