STUDIES OF CHRONIC MORPHINE POISONING IN DOGS V. RECOVERY OF MORPHINE FROM THE TISSUES OF TOLERANT AND NON-TOLERANT ANIMALS

¹ From the Laboratory of Pharmacology, State University of Iowa, Iowa City, Iowa

1. A method is described for the extraction and estimation of small amounts of morphine, which gave consistent results (95 to 110 per cent recovery) when the alkaloid is added to normal tissues.

2. Results are given for the recovery of morphine from liver, muscle, central nervous system, heart, lungs, and blood and from the excretory organs and excretions of twenty-four dogs, half of which had received a single dose of morphine, and half had received daily a dose of the same size for periods of approximately one year to more than four years. Tissues from an equal number of both tolerant and non-tolerant dogs were analysed four hours and twenty-four hours after the dose. The tissues and body fluids sampled amounted to 54 to 56 per cent of the body weight.

3. The average total recovery from the six tissues examined four hours after the dose was greater (42.8 per cent) in the non-tolerant dogs, while in the same tissues examined twenty-four hours after the dose the average total recovery was greater (46.2 per cent) in the tolerant animals. The average concentration in these tissues showed the same type of difference.

4. Of the individual tissues, muscle yielded the largest amounts but the concentration in muscle was of the same order as the other tissues. The central nervous system in the tolerant dog contained less than the non-tolerant ones. The blood of tolerant animals contained more than of non-tolerant. The average concentration in the liver was greater than in the other tissues.

5. The amount of morphine in the kidneys and urine was practically the same in tolerant and non-tolerant dogs at the end of four hours, but it was greater in the tolerant dogs at the end of twenty-four hours. The alimentary canal and its contents yielded much more morphine in the tolerant animals than in the non-tolerant ones in both the four hour and in the twenty-four hour group.

6. The percentage of the dose recovered in the tissues and excretory organs of non-tolerant animals was distinctly less in the twenty-four hour group than in the four hour group, while in the tolerant dogs the percentage of the dose recovered was greater twenty-four hours after the dose.

7. The results suggest there is a difference in the manner in which morphine is handled in tolerant and non-tolerant dogs. The larger amounts recovered from tolerant animals, as compared with non-tolerant ones, twenty-four hours after the dose, indicates that increased ability to "destroy" morphine is not a factor in tolerance. There is some evidence of storage of morphine in the tissues as well as in the alimentary canal.