, Volume 39, Issue 2, pp 151–162 | Cite as

Antagonism of morphine by long acting narcotic antagonists

  • Linda A. Dykstra
  • D. E. McMillan
  • L. S. Harris
Animal Studies


The effects of three narcotic antagonists, diprenorphine, naltrexone, and naloxone were studied on the schedule-controlled behavior of pigeons. Naltrexone decreased the rate of responding under the FR and FI components of a multiple fixed-interval, fixed-ratio schedule. Naltrexone and diprenorphine were equipotent in blocking the rate-decreasing effects of morphine on schedule-controlled behavior when the antagonists were given immediately before morphine, and both were more potent morphine antagonists than naloxone. Higher doses of all 3 antagonists were required to block the effects of morphine as the time between the administration of the antagonist and morphine increased. Naltrexone provided a slightly better antagonism of morphine than diprenorphine when morphine was given 2 or 6 h after the antagonist and both antagonists had a longer duration of antagonist action than naloxone.

Key words

Morphine Naloxone Naltrexone Diprenorphine Antagonists Pigeon Multiple Schedule 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Blane, G. F., Boura, A. L.: Analgesic and other actions of morphine antagonists. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. 259, 154–155 (1967)Google Scholar
  2. Blane, G. F., Dugdall, D.: Interaction of narcotic antagonists and antagonist-analgesics. J. Pharm. Pharmacol. 20, 547 (1968)Google Scholar
  3. Blumberg, H., Dayton, H. B.: Narcotic antagonist studies with EN-1639 A (N-cyclopropylmethylnoroxymorphone hydrochloride). Fifth International Congress on Pharmacology 23 (1972)Google Scholar
  4. Blumberg, H., Dayton, H. B. G., Wolf, P. S.: Analgesic and narcotic antagonist properties of noroxymorphone derivatives. Toxicol. appl. Pharmacol. 10, 406 (1967)Google Scholar
  5. Blumberg, H., Dayton, H. B., Wolf, P. S.: Counteraction of narcotic antagonist analgesics by the narcotic antagonist naloxone. Proc. Soc. exp. Biol. (N. Y.) 123, 755–758 (1966)Google Scholar
  6. Cowan, A.: Evaluation of nonhuman primates: evaluation of the physical dependence capacities of oripavine-thebaine partial agonists in patas monkeys. In: Narcotic Antagonists. New York: Raven Press 1973Google Scholar
  7. Ferster, C. B., Skinner, B. F.: Schedules of reinforcement. New York: Appleton Century-Crofts 1957Google Scholar
  8. Gollub, L. R.: The relations among measures of performance of fixed-interval schedules. J. exp. Anal. Behav. 7, 337–343 (1964)Google Scholar
  9. Hammond, A. L.: Narcotic antagonists: new methods to treat heroin addiction. Science 173, 503–506 (1971)Google Scholar
  10. Jasinski, D. R., Martin, W. R., Haertzen, C. A.: The human pharmacology and abuse potential of n-allylnoroxymorphone (naloxone). J. Pharmacol. exp. Ther. 157, 420–426 (1967)Google Scholar
  11. Kosterlitz, H. W., Waterfield, A. A., Berthoud, V.: Assessment of the agonist and antagonist properties of narcotic analgesic drugs by their actions on the morphine receptor in guinea-pig ileum. In: Narcotic Antagonists. New York: Raven Press 1973Google Scholar
  12. Lasagna, L., Beecher, H. K.: The analgesic effectiveness of nalorphine and nalorphine-morphine combinations in man. J. Pharmacol. exp. Ther. 112, 356–363 (1954)Google Scholar
  13. Martin, W. R.: Opoid antagonists. Pharmacol. Rev. 19, 463–522 (1967)Google Scholar
  14. Martin, W. R., Gorodetzky, C. W.: Cyclazocine, an adjunct in the treatment of narcotic addiction. Int. J. Addict. 2, 85–93 (1967)Google Scholar
  15. Martin, W. R., Gorodetzky, C. W., McClane, T. K.: An experimental study in the treatment of narcotic addicts with cyclazocine. Clin. Pharmacol. Ther. 7, 453–465 (1966)Google Scholar
  16. Martin, W. R., Jasinski, D. R., Mansky, P. A.: Naltrexone, an antagonist for the treatment of heroin dependence. Arch. gen. Psychiat. 28, 784–791 (1973)Google Scholar
  17. McMillan, D. E.: Effects of narcotics and narcotic antagonists on operant behavior. In: Narcotic Antagonists. New York: Raven Press 1973Google Scholar
  18. McMillan, D. E., Harris, L. S.: Behavioral and morphine-antagonist effects of the optical isomers of pentazocine and cyclazocine. J. Pharmacol. exp. Ther. 180, 269–279 (1972)Google Scholar
  19. McMillan, D. E., Morse, W. H.: Some effects of morphine and morphine antagonists on schedule-controlled behavior. J. Pharmacol. exp. Ther. 157, 175–184 (1967)Google Scholar
  20. McMillan, D. E., Wolf, P. S., Carchman, P. S.: Antagonism of the behavioral effects of morphine and methadone by narcotic antagonists in the pigeon. J. Pharmacol. exp. Ther. 175, 443–458 (1970)Google Scholar
  21. Orahovats, P. D., Winter, C. A., Lehman, E. G.: The effect of n-allylnormorphine upon the development of tolerance to morphine in the albino rat. J. Pharmacol. exp. Ther. 109, 413–416 (1953)Google Scholar
  22. Takemori, A. E., Hayashi, G.: Quantitative antagonism of morphine, pentazocine and etorphine (M99) by naloxone and diprenorphine (M5050). Pharmacologist 12, 210 (1970)Google Scholar
  23. Takemori, A. E., Hayashi, G., Smits, S. E.: Studies on the quantitative antagonism of analgesics by naloxone and diprenorphine. Europ. J. Pharmacol. 20, 85–92 (1972)Google Scholar
  24. Villarreal, J. E., Karbowski, M. G.: The actions of narcotic antagonists in morphine-dependent rhesus monkeys. In: Narcotic Antagonists. New York: Raven Press 1973Google Scholar
  25. Woods, L. A.: The pharmacology of nalorphine (n-allylnormorphine). Pharmacol. Rev. 8, 175–198 (1956)Google Scholar

Copyright information

© Springer-Verlag 1974

Authors and Affiliations

  • Linda A. Dykstra
    • 1
    • 2
  • D. E. McMillan
    • 2
  • L. S. Harris
    • 2
  1. 1.The Department of PsychologyUniversity of North CarolinaChapel Hill
  2. 2.Department of PharmacologyUniversity of North CarolinaUSA

Personalised recommendations