DISTRIBUTION OF N-C¹⁴-METHYL LABELED MORPHINE: I. IN CENTRAL NERVOUS SYSTEM OF NONTOLERANT AND TOLERANT DOGS

¹ Department of Pharmacology and Toxicology, University of Wisconsin, Madison, Wisconsin
² Department of Pharmacology, College of Medicine, State University of Iowa, Iowa City, Iowa

A method is described for the estimation of N-C¹⁴-methyl labeled morphine in biological materials, which is sensitive to a level of 4 to 5 millimicrograms.

Concentrations of free labeled morphine were lower in the CNS of tolerant dogs in comparison to nontolerant dogs at various intervals of time after a single 2-mg/kg subcutaneous injection of labeled drug.

The levels of free morphine in the CNS of tolerant dogs following consecutive 2-mg/kg subcutaneous injections as compared to consecutively injected nontolerant dogs were higher at 35 minutes, similar at 4 hours, and much lower at 8 hours.

Generally, the cerebral cortical gray matter contained the highest concentrations of free morphine in both nontolerant and tolerant dogs. Predominantly cellular subcortical areas of the CNS occasionally contained levels of free morphine equal to cerebral gray matter values. Cerebral and cerebellar white matter levels of free morphine were lower than gray during the early time intervals and approximately the same as gray matter or higher at later time periods. Small quantities of conjugated morphine were observed in the temporal cortex of nontolerant and tolerant dogs.

The rate of disappearance of free morphine from plasma and CSF was faster in tolerant than in nontolerant dogs following a single injection of labeled morphine. Egression of free morphine from plasma and CSF following consecutive labeled morphine injections were quite similar in nontolerant and tolerant dogs. Conjugated morphine levels in plasma were much lower in tolerant dogs as compared to corresponding values in nontolerant dogs after consecutive injections.

The differences in the physiological disposition of free morphine between nontolerant and tolerant dogs do not appear to be of sufficient magnitude to account for tolerance development.

This article has been cited by other articles:

				C. Breitfeld, J. Peters, T. Vockel, C. Lorenz, and M. Eikermann Emetic effects of morphine and piritramide Br. J. Anaesth., August 1, 2003; 91(2): 218 - 223. [Abstract] [Full Text] [PDF]

				L. D. Napier, A. Stanfill, D. A. Yoshishige, K. E. Jackson, B. A. Barron, and J. L. Caffrey Autonomic control of heart rate in dogs treated chronically with morphine Am J Physiol Heart Circ Physiol, December 1, 1998; 275(6): H2199 - H2210. [Abstract] [Full Text] [PDF]

				D. Lange, S. Roerig, J. Fujimoto, and R. Wang Absence of cross-tolerance to heroin in morphine-tolerant mice Science, April 4, 1980; 208(4439): 72 - 74. [Abstract] [PDF]