Abstract
The tolerance phenomenon to drugs has always been an intriguing problem. From a review of the literature, two hypotheses have been retained and discussed; none seems to bring a satisfactory explanation.
The work of Beutner and of Van Leuween around 1925 has inspired the authors who devised an experiment with two groups of dogs, one receiving progressively greater quantities of morphine, the other one receiving no medication. They succeeded in measuring the amount of morphine linked to an hypothetic plasma protein and tried to establish how this correlates with the tolerance phenomenon. They feel this protein fixation of morphine in plasma plays an important role in the tolerance acquisition to drugs. The amount of medication reaching the blood-brain barrier is affected by this process as well as the following excretion time of the drug.
The results have confirmed the authors' hypotheses; in a next step they will attempt to isolate and identify the specific plasma protein involved. Research on cerebro-spinal fluid has not yielded any information on the diffusion time of the drug in the two groups of dogs: morphine could not be detected probably because of its great affinity for the surrounding structures.