ACTIVE REMOVAL OF MORPHINE FROM THE CEREBRAL VENTRICLES

¹ Department of Pharmacology, University of California Medical Center, San Francisco, California

The removal of N-C¹⁴-labeled morphine from the cerebral ventricles was studied by continuous ventricular perfusion in anesthetized as well as in conscious rabbits. The concentration of morphine in the influent and effluent fluids was determined by liquid scintillation counting, and the percentage of morphine removed was calculated after correcting for the dilution of the perfused fluid by the freshly formed cerebrospinal fluid. Morphine was found to be actively removed from the perfusion fluid during its passage through the cerebroventricular spaces. The removal of morphine followed saturation kinetics and was diminished by concurrent perfusion of structurally related compounds. The energy dependence of the process was evidenced by the lack of morphine removal from the perfusion fluid in the dead rabbit and almost complete inhibition of removal by ouabain. The results suggest that the transport process is intricately linked to the Na⁺,K⁺-activated adenosine triphosphatase system. Since only 25% of the total morphine extracted from the perfusion fluid could be found in the whole brain and the choroid plexi, the remainder of the morphine was probably transported into the blood after its removal from the ventricular system by the choroid plexus.