DISTRIBUTION OF N-C¹⁴-METHYL LABELED MORPHINE. III. EFFECT OF NALORPHINE IN THE CENTRAL NERVOUS SYSTEM AND OTHER TISSUES OF TOLERANT DOGS

¹ U. S. Department of Health, Education, and Welfare, Public Health Service, National Institute of Mental Health, Addiction Research Center, Lexington, Kentucky

The administration of 2 mg/kg of N-C¹⁴- methyl labeled morphine to tolerant dogs, followed in 35 minutes by 2 mg/kg of nonlabeled nalorphine, resulted in a statistically significant decrease (42 to 56%) in central nervous system levels of morphine at 65 minutes, and no real change at either 165 or 275 minutes following the labeled drug.

Nalorphine caused a reduction of 5 to 73% in the levels of morphine at each time interval in the heart, lung, liver and kidney.

Chromatographic studies of the central nervous system extracts of nalorphine antagonized dogs provided no evidence for the existence of an N-C¹⁴-methyl labeled metabolite of morphine.

The plasma levels of free morphine in the nalorphine antagonized dog were essentially lower than control values between 30 and 275 minutes following drug administration. Conjugated morphine levels in the plasma were lower in control animals as compared to the antagonized dogs between 60 and 180 minutes after labeled morphine, and similar between 180 and 275 minutes.

The CSF levels of morphine in the antagonized dogs were lower than control levels at 65 and 275 minutes following drug administration.