CENTRAL NERVOUS SYSTEM DISTRIBUTION AND METABOLISM OF C¹⁴-MORPHINE DURING MORPHINE-INDUCED FELINE MANIA

¹ Department of Pharmacology, University of Iowa Medical School, Iowa City, Iowa

The purpose of this investigation was to attempt a correlation of the central nervous system distribution of morphine with the mania this drug produces in cats. Results obtained were compared to those reported for the dog, a species in which CNS depression is the pharmacological response to morphine. Generally, gray matter in both species contained the highest concentration of free morphine. No consistent differences were noted in comparing drug concentrations in various selected areas of the central nervous system of the two species. The only CNS differences between the species were time-distribution patterns. Brain levels in the dog rise to peak at one-half hour and remain relatively constant for 8 hours, whereas in the cat, maximum concentrations were at 2 hours with 8-hour values approximately those observed at one-half hour.

Conclusions drawn were that differences in the central nervous system distribution of morphine did not explain the difference in overt responses between the cat and dog.

Highest plasma levels of free morphine were at one-half hour in both species and were approximately equal; subsequently, the levels in the cat were higher.

Biliary excretion of morphine in the cat is a significant but not prominent avenue of detoxication since no more than 10% of the administered dose, with a significant proportion of this being free drug, was found in the bile. Excretion of morphine and its conjugate via the kidneys is a major pathway in the cat as has been shown for other species.