SOME FACTORS AFFECTING THE BIOLOGICAL DISPOSITION OF SMALL DOSES OF MORPHINE IN RATS

¹ Departments of Pharmacology and Experimental Therapeutics, and Anesthesiology, University of California Medical Center, San Francisco

The metabolic fate of small doses of C¹⁴-labeled morphine in rats as influenced by adrenalectomy or pretreatment with ACTH or vasopressin has been studied utilizing isotope dilution and paper chromatography techniques. The principal findings were as follows:

The ratio of bound to free morphine is 2 to 3 times greater in the urine and plasma of Sprague-Dawley rats than in Long-Evans rats on the same dose.

The C¹⁴ content of plasma can be almost completely accounted for as free and bound morphine but a substantial fraction of that present in brain and muscle remains unidentified as does a very small fraction in urine of Long-Evans rats.

The tissues of adrenalectomized rats, of both strains, contain higher concentrations of C¹⁴ after morphine-N-C¹⁴H₃ administration than do control rats. Plasma bound morphine levels indicate no impairment in the ability of these animals to conjugate morphine.

Although vasopressin increases the sensitivity of rats to morphine, tissue concentrations after pretreatment with vasopressin are either reduced or relatively unaffected in marked contrast to the increased values after adrenalectomy.

Tissue C¹⁴ levels after ACTH are similar to those after vasopressin. Thus decreased sensitivity to morphine due to ACTH is not reflected in lower brain C¹⁴ concentrations.

None of the treatments appear to affect the absorption of the dose or urinary excretion at sixty minutes after injection.