EFFECT OF NALOXONE ON THE MORPHINE CONCENTRATION IN THE CENTRAL-NERVOUS-SYSTEM AND PLASMA IN RATS

We investigated whether the distribution (concentration) of morphine i n the central nervous system (CNS) after systemic administration could be an index for the in vivo binding of morphine. Neither the morphine concentration nor its decline correlated with the density of opiate r eceptors. Naloxone decreased the morphine concentration in some CNS re gions and plasma after a high dose of morphine, but not after a small dose of morphine. The CNS regions in which naloxone decreased the morp hine concentration did not correlate with the density of opiate recept ors, and the concentration ratios (CNS regions versus plasma) of morph ine were not affected by naloxone. These results suggested that the mo rphine concentration in the CNS did not reflect the in vivo binding of morphine and that the naloxone-induced decrease in morphine concentra tion was not due to a displacement of morphine from its receptor sites but due to a change in morphine kinetics. Pharmacokinetic studies sug gested that naloxone decreased the morphine concentration through an i ncreased volume of morphine distribution. This naloxone-induced decrea se in morphine concentration may contribute to the naloxone-induced in hibition of morphine action in addition to the competitive antagonism at opiate receptors.