STUDIES ON THE TRANSPORT OF MORPHINE INTO THE CEREBROSPINAL FLUID OF RABBITS1

WANG, J. H. AND A. E. TuEMoRI: Studies on the transport of morphine into the cerebrospinal fluid of rabbits. J. Pharmacol. Exp. Ther. 183: 41-48, 1972. The transport of morphine from the systemic circulation into the perfused cerebrospinal fluid was studied while the free morphine plasma concentration was kept constant with continuous infusion in rabbits whose renal vessels had been ligated. The transport of morphine into the cerebrospinal fluid from blood appeared to be a carrier-mediated proc-ess since morphine was transported against a concentration gradient and the transport was inhibited by compounds structurally related to morphine such as codeine, ethyl-morphine, nalorphine and naloxone. Morphine transport was also inhibited by sys-temically administered organic basic compounds such as N-methylnicotinamide and SKF 525A and by dinitrophenol. Our previous study showed that morphine passively diffused out of the perfused ventricles in rabbits (Wang and Takemori, 1972). It was now of interest to determine by what process morpine was transported from the systemic cir-culation into the cerebrospinal fluid (CSF). The data in the present study indicate that morphine is transported into the perfused CSF from blood possibly by a carrier-mediated process and evi-dence for this conclusion is reported herein. The possible relationship of this transport system to the development of tolerance to morphine was also studied. Received for publication March 13, 1972. 1This investigation was supported by U.S. Public Health Service Grant GM 15477. A pre-liminary report was presented at the annual meet