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. 1979;7(Suppl 3):297S–308S. doi: 10.1111/j.1365-2125.1979.tb04704.x

Analgesic effectiveness of the narcotic agonist-antagonists

Raymond W Houde
PMCID: PMC1429304  PMID: 223617

Abstract

1 Two fundamentally different types of narcotic-antogonists have been found to be very effective analgesics with relatively low dependence-producing potentials.

2 These two drug classes can be distinguished as being either morphine-like or nalorphine-like on the basis of their subjective and objective effects after single doses and on chronic administration, and by the character of their abstinence syndromes on abrupt withdrawal or on precipitation by other antagonists.

3 To explain differences in side effects associated with their analgesic actions, the existence of three types of receptors has been postulated: a μ receptor which is believed to be associated with euphoria and other typical morphine-like effects and a kappa (χ) and a sigma (σ) receptor which are believed to be associated with the sedative and psychotomimetic effects, respectively, of the nalorphine-like drugs.

4 The antagonist-analgesics of the morphine-type have the characteristics of being agonists of low intrinsic activity but with high affinity for the μ receptor. Representative analgesics of this type are profadol, propiram and buprenorphine.

5 The antagonist-analgesics of the nalorphine-type are drugs which are believed to have varying degrees of affinity and intrinsic activity at all three receptors, but characteristically seem to act merely as competitive antagonists with no intrinsic activity at the μ receptor. Representative analgesics of this type are pentazocine, nalbuphine and butorphanol.

6 There are considerable differences among the individual drugs of each type in terms of their analgesic and narcotic-antagonistic potencies. However, clear differences in analgesic efficacy among any of the antagonist-analgesics remain to be proved. All give evidence of being capable of relieving pain in nondependent patients in situations in which doses of morphine (or its surrogates) usually used would be effective.

7 The major advantages of the partial agonists of the morphine-type over the nalorphine-type drugs are that they have not been found to produce psychotomimetic reactions, and they seem to have fewer potentially deleterious effects in cardiac patients.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ARCHER S., ALBERTSON N. F., HARRIS L. S., PIERSON A. K., BIRD J. G., KEATS A. S., TELFORD J., PAPADOPOULOS C. N. Narcotic antagonists as analgesics. Science. 1962 Aug 17;137(3529):541–543. doi: 10.1126/science.137.3529.541. [DOI] [PubMed] [Google Scholar]
  2. Alderman E. L., Barry W. H., Graham A. F., Harrison D. C. Hemodynamic effects of morphine and pentazocine differ in cardiac patients. N Engl J Med. 1972 Sep 28;287(13):623–627. doi: 10.1056/NEJM197209282871301. [DOI] [PubMed] [Google Scholar]
  3. Beaver W. T., Wallenstein S. L., Houde R. W., Rogers A. A clinical comparison of the effects of oral and intramuscular administration of analgesics: pentazocine and phenazocine. Clin Pharmacol Ther. 1968 Sep-Oct;9(5):582–597. doi: 10.1002/cpt196895582. [DOI] [PubMed] [Google Scholar]
  4. Beaver W. T., Wallenstein S. L., Houde R. W., Rogers A. A comparison of the analgesic effects of pentazocine and morphine in patients with cancer. Clin Pharmacol Ther. 1966 Nov-Dec;7(6):740–751. doi: 10.1002/cpt196676740. [DOI] [PubMed] [Google Scholar]
  5. Beaver W. T., Wallenstein S. L., Houde R. W., Rogers A. A comparison of the analgesic effects of profadol and morphine in patients with cancer. Clin Pharmacol Ther. 1969 May-Jun;10(3):314–319. doi: 10.1002/cpt1969103314. [DOI] [PubMed] [Google Scholar]
  6. Brogden R. N., Speight T. M., Avery G. S. Pentazocine: a review of its pharmacological properties, therapeutic efficacy and dependence liability. Drugs. 1973;5(1):6–91. doi: 10.2165/00003495-197305010-00002. [DOI] [PubMed] [Google Scholar]
  7. CASS L. J., FREDERIK W. S., TEODORO J. V. PENTAZOCINE AS AN ANALGESIC. CLINICAL EVALUATION. JAMA. 1964 Apr 13;188:112–115. doi: 10.1001/jama.1964.03060280014003. [DOI] [PubMed] [Google Scholar]
  8. Cowan A., Doxey J. C., Harry E. J. The animal pharmacology of buprenorphine, an oripavine analgesic agent. Br J Pharmacol. 1977 Aug;60(4):547–554. doi: 10.1111/j.1476-5381.1977.tb07533.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. DUNDEE J. W. A CLINICAL TRIAL OF A MIXTURE OF LEVORPHANOL AND LEVALLORPHAN AS AN ORAL ANALEGESIC. Br J Anaesth. 1964 Aug;36:486–493. doi: 10.1093/bja/36.8.486. [DOI] [PubMed] [Google Scholar]
  10. Delpizzo A. Butorphanol, a new intravenous analgesic: double-blind comparison with morphine sulfate in postoperative patients with moderate or severe pain. Curr Ther Res Clin Exp. 1976 Sep;20(3):221–232. [PubMed] [Google Scholar]
  11. Dobkin A. B., Eamkaow S., Caruso F. S. Butorphanol and pentazocine in patients with severe postoperative pain. Clin Pharmacol Ther. 1975 Nov;18(5 Pt 1):547–553. doi: 10.1002/cpt1975185part1547. [DOI] [PubMed] [Google Scholar]
  12. Dobkin A. B., Esposito B., Philbin C. Double-blind evaluation of buprenorphine hydrochloride for post-operative pain. Can Anaesth Soc J. 1977 Mar;24(2):195–202. doi: 10.1007/BF03006232. [DOI] [PubMed] [Google Scholar]
  13. Downing J. W., Leary W. P., White E. S. Buprenorphine: a new potent long-acting synthetic analgesic. Comparison with morphine. Br J Anaesth. 1977 Mar;49(3):251–255. doi: 10.1093/bja/49.3.251. [DOI] [PubMed] [Google Scholar]
  14. Elliott H. W., Navarro G., Nomof N. A double blind controlled study of the pharmacologic effects of nalbuphine (EN-2234A). J Med. 1970;1(2):74–89. [PubMed] [Google Scholar]
  15. Engineer S., Jennett S. Respiratory depression following single and repeated doses of pentazocine and pethidine. Br J Anaesth. 1972 Aug;44(8):795–802. doi: 10.1093/bja/44.8.795. [DOI] [PubMed] [Google Scholar]
  16. FOLDES F. F., LUNN J. N., MOORE J., BROWN I. M. N-Allylnoroxy-morphone: a new potent narcotic antagonist. Am J Med Sci. 1963 Jan;245:23–30. [PubMed] [Google Scholar]
  17. Fraser H. F., Harris L. S. Narcotic and narcotic antagonist analgesics. Annu Rev Pharmacol. 1967;7:277–300. doi: 10.1146/annurev.pa.07.040167.001425. [DOI] [PubMed] [Google Scholar]
  18. GRUBER C. M., Jr The effect of N-allylnormorphine upon the toxicity of morphine. J Pharmacol Exp Ther. 1954 Aug;111(4):404–408. [PubMed] [Google Scholar]
  19. Gilbert M. S., Forman R. S., Moylan D. S., Caruso F. S. Butorphanol: a double-blind comparison with pentazocine in post-operative patients with moderate to severe pain. J Int Med Res. 1976;4(4):255–264. doi: 10.1177/030006057600400408. [DOI] [PubMed] [Google Scholar]
  20. Gilbert M. S., Hanover R. M., Moylan D. S., Caruso F. S. Intramuscular butorphanol and meperidine in postoperative pain. Clin Pharmacol Ther. 1976 Sep;20(3):359–364. doi: 10.1002/cpt1976203359. [DOI] [PubMed] [Google Scholar]
  21. Gilbert P. E., Martin W. R. The effects of morphine and nalorphine-like drugs in the nondependent, morphine-dependent and cyclazocine-dependent chronic spinal dog. J Pharmacol Exp Ther. 1976 Jul;198(1):66–82. [PubMed] [Google Scholar]
  22. Hamilton R. C., Dundee J. W., Clarke R. S., Loan W. B., Morrison J. D. Studies of drugs given before anaesthesia. 13. Pentazocine and other opiate antagonists. Br J Anaesth. 1967 Aug;39(8):647–656. doi: 10.1093/bja/39.8.647. [DOI] [PubMed] [Google Scholar]
  23. ISBELL H., FRASER H. F. Addiction to analgesics and barbiturates. J Pharmacol Exp Ther. 1950 Aug;99(42):355–397. [PubMed] [Google Scholar]
  24. ISBELL H. The search for a nonaddicting analgesic. J Am Med Assoc. 1956 Jul 28;161(13):1254–1254. doi: 10.1001/jama.1956.02970130042011. [DOI] [PubMed] [Google Scholar]
  25. Isbell H. The search for a nonaddicting analgesic: has it been worth it? The twenty-third Oscar B. Hunter Memorial Award in Therapeutics lecture. Clin Pharmacol Ther. 1977 Oct;22(4):377–384. doi: 10.1002/cpt1977224377. [DOI] [PubMed] [Google Scholar]
  26. Jasinski D. R., Mansky P. A. Evaluation of nalbuphine for abuse potential. Clin Pharmacol Ther. 1972 Jan-Feb;13(1):78–90. doi: 10.1002/cpt197213178. [DOI] [PubMed] [Google Scholar]
  27. Jasinski D. R., Martin W. R., Hoeldtke R. Studies of the dependence-producing properties of GPA-1657, profadol, and propiram in man. Clin Pharmacol Ther. 1971 Jul-Aug;12(4):613–649. doi: 10.1002/cpt1971124613. [DOI] [PubMed] [Google Scholar]
  28. Jasinski D. R., Martin W. R., Sapira J. D. Antagonism of the subjective, behavioral, pupillary, and respiratory depressant effects of cyclazocine by naloxone. Clin Pharmacol Ther. 1968 Mar-Apr;9(2):215–222. doi: 10.1002/cpt196892215. [DOI] [PubMed] [Google Scholar]
  29. Jasinski D. R., Pevnick J. S., Griffith J. D. Human pharmacology and abuse potential of the analgesic buprenorphine: a potential agent for treating narcotic addiction. Arch Gen Psychiatry. 1978 Apr;35(4):501–516. doi: 10.1001/archpsyc.1978.01770280111012. [DOI] [PubMed] [Google Scholar]
  30. KEATS A. S., TELFORD J. Nalorphine, a potent analgesic in man. J Pharmacol Exp Ther. 1956 Jun;117(2):190–196. [PubMed] [Google Scholar]
  31. KEATS A. S., TELFORD J. STUDIES OF ANALGESIC DRUGS. VIII. A NARCOTIC ANTAGONIST ANALGESIC WITHOUT PSYCHOTOMIMETIC EFFECTS. J Pharmacol Exp Ther. 1964 Feb;143:157–164. [PubMed] [Google Scholar]
  32. KEATS A. S., TELFORD J. Subjective effects of nalorphine in hospitalized patients. J Pharmacol Exp Ther. 1957 Mar;119(3):370–377. [PubMed] [Google Scholar]
  33. LANDMESSER C. M., COBB S., CONVERSE J. G. Effects of N-allylnormorphine upon the respiratory depression due to morphine in anesthetized man with studies on the respiratory response to carbon dioxide. Anesthesiology. 1953 Nov;14(6):535–549. doi: 10.1097/00000542-195311000-00001. [DOI] [PubMed] [Google Scholar]
  34. LASAGNA L., BEECHER H. K. The analgesic effectiveness of nalorphine and nalorphine-morphine combinations in man. J Pharmacol Exp Ther. 1954 Nov;112(3):356–363. [PubMed] [Google Scholar]
  35. LASAGNA L., DEKORNFELD T. J., PEARSON J. W. THE ANALGESIC EFFICACY AND RESPIRATORY EFFECTS IN MAN OF A BENZOMORPHAN "NARCOTIC ANTAGNOST". J Pharmacol Exp Ther. 1964 Apr;144:12–16. [PubMed] [Google Scholar]
  36. LASAGNA L. THE CLINICAL EVALUATION OF MORPHINE AND ITS SUBSTITUTES AS ANALGESICS. Pharmacol Rev. 1964 Mar;16:47–83. [PubMed] [Google Scholar]
  37. Martin W. R., Eades C. G., Thompson J. A., Huppler R. E., Gilbert P. E. The effects of morphine- and nalorphine- like drugs in the nondependent and morphine-dependent chronic spinal dog. J Pharmacol Exp Ther. 1976 Jun;197(3):517–532. [PubMed] [Google Scholar]
  38. Martin W. R., Fraser H. F., Gorodetzky C. W., Rosenberg D. E. Studies of the dependence-producing potential of the narcotic antagonist 2-cyclopropylmethyl-2'-hydroxy-5,9-dimethyl-6,7-benzomorphan (cyclazocine, WIN-20,740, ARC II-c-3). J Pharmacol Exp Ther. 1965 Dec;150(3):426–436. [PubMed] [Google Scholar]
  39. Martin W. R. Opioid antagonists. Pharmacol Rev. 1967 Dec;19(4):463–521. [PubMed] [Google Scholar]
  40. Nagashima H., Karamanian A., Malovany R., Radnay P., Ang M., Koerner S., Foldes F. F. Respiratory and circulatory effects of intravenous butorphanol and morphine. Clin Pharmacol Ther. 1976 Jun;19(6):738–745. doi: 10.1002/cpt1976196738. [DOI] [PubMed] [Google Scholar]
  41. Popio K. A., Jackson D. H., Ross A. M., Schreiner B. F., Yu P. N. Hemodynamic and respiratory effects of morphine and butorphanol. Clin Pharmacol Ther. 1978 Mar;23(3):281–287. doi: 10.1002/cpt1978233281. [DOI] [PubMed] [Google Scholar]
  42. Rolly G., Versichelen L. Buprenorphine as postoperative analgesic. Acta Anaesthesiol Belg. 1976;27(3):183–186. [PubMed] [Google Scholar]
  43. Stoelting V. K. Analgesic action of pentazocine compared with morphine in postoperative pain. Anesth Analg. 1965 Nov-Dec;44(6):769–772. [PubMed] [Google Scholar]
  44. TELFORD J., PAPADOPOULOS C. N., KEATS A. S. Studies of analgesic drugs. VII. Morphine antagonists as analgesics. J Pharmacol Exp Ther. 1961 Jul;133:106–116. [PubMed] [Google Scholar]
  45. Tavakoli M., Corssen G., Caruso F. S. Butorphanol and morphine: a double-blind comparison of their parenteral analgesic activity. Anesth Analg. 1976 May-Jun;55(3):394–401. doi: 10.1213/00000539-197605000-00025. [DOI] [PubMed] [Google Scholar]
  46. WIKLER A., FRASER H. F., ISBELL H. N-Allylnormorphine: effects of single doses and precipitation of acute abstinence syndromes during addiction to morphine; methadone or heroin in man (post addicts). J Pharmacol Exp Ther. 1953 Sep;109(1):8–20. [PubMed] [Google Scholar]
  47. YIM G. K., KEASLING H. H., GROSS E. G., MITCHELL C. W. Simultaneous respiratory minute volume and tooth pulp threshold changes following levorphan, morphine and levorphan-levallorphan mixtures in rabbits. J Pharmacol Exp Ther. 1955 Sep;115(1):96–105. [PubMed] [Google Scholar]

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