A COMPARISON OF THE PHARMACOLOGIC EFFECTS OF MORPHINE AND N-METHYL MORPHINE

¹ Department of Pharmacology, School of Medicine and the Brain Research Institute, University of California, Los Angeles, California

The pharmacologic effects of N-methyl morphine are quite different from those produced by morphine when the drugs are administered systemically. The only obvious effect noted with the quaternary derivative is neuromuscular paralysis, and death may result from respiratory failure. Further investigation of the drugs revealed that both lead to depression of intestinal motility when given intravenously. Analgesia and hypothermia do not appear following systemic injection of N-methyl morphine in doses that produce marked effects in the case of morphine. Injection of either drug into the thermoregulatory centers of the rat leads to a fall in core temperature and both can produce analgesia when injected directly into the region of the periventricular gray matter. When compared in their actions on peripheral structures, qualitatively similar effects were noted on the superior cervical ganglion of the cat and the isolated guinea-pig ileum in blocking the response to muscarinic drugs and coaxial electrical stimulation respectively. In most instances the N-methyl compound is somewhat less active than morphine. It is concluded that the modification of the morphine molecule does not necessarily destroy its pharmacologic actions once it has access to its receptor sites but the profound differences reported previously are due mainly to the inability of the charged N-methyl molecule to enter the central nervous system.

This article has been cited by other articles:

				D. J. Mayer, T. L. Wolfle, H. Akil, B. Carder, and J. C. Liebeskind Analgesia from Electrical Stimulation in the Brainstem of the Rat Science, December 24, 1971; 174(4016): 1351 - 1354. [Abstract] [PDF]