, Volume 38, Issue 2, pp 226–248 | Cite as


A Preliminary Review of its Pharmacodynamic and Pharmacokinetic Properties, and Therapeutic Efficacy
  • John J. O’Brien
  • Paul Benfield
Drug Evaluation



Dezocine is an analgesic agent with opioid agonist and antagonist activity. After parenteral administration of therapeutic doses it is approximately equipotent with morphine, and has proved at least as effective an analgesic as morphine, pethidine (meperidine) and butorphanol in moderate to severe postoperative pain. However, preliminary pharmacodynamic data indicate that the ceiling of analgesic activity of dezocine occurs at a higher level of analgesia than that of reference agonist/antagonist agents. Also, the drug exhibited a morphine-like degree of anaesthetic-sparing activity in animals.

Although long term data are very limited, single doses of dezocine are well tolerated, with mild and transient sedation and gastrointestinal upset the principal adverse effects. As with some other agonist/antagonist analgesics, a ‘ceiling’ effect to dezocine-induced respiratory depression occurs with increasing dosage, beyond which further depression has not been observed. In single analgesic doses, however, dezocine is a slightly more potent respiratory depressant than morphine. Clinically important haemodynamic changes have not been observed with usual analgesic doses of dezocine.

As an agonist/antagonist opioid, the dependence liability of dezocine would be expected to be lower than that of pure agonist opioids, but extended clinical use is required before more definitive conclusions can be drawn in this regard. Unlike older drugs of its type, dezocine produced opiate-like subjective effects and was identified as morphine-like by drug abusers.

Thus, provided the promising conclusions of currently available clinical studies are confirmed with its wider use, dezocine should be a useful additional agent for the treatment of moderate to severe postoperative pain.

Pharmacodynamic Properties

The opioid agonist activity of dezocine has been demonstrated in tests of analgesia in rodents and monkeys, in which the drug proved substantially more potent than standard centrally acting analgesics such as morphine, codeine and pentazocine. In animal behavioural tests, dezocine acted as a positive reinforcer, and shared discriminative stimulus properties with morphine and etorphine, but not ethylketazocine. As with several other drugs of this class, dezocine proved relatively resistant to reversal by classic opioid antagonists in animal models. However, its effects are fully reversible with naloxone in humans. Successive intravenous doses of dezocine 0.15 mg/kg in healthy volunteers produced a ceiling or plateau in the analgesic effect at 0.30 mg/kg, with further doses failing to increase the level of analgesia. In clinical studies of postoperative pain, dezocine provided dose-dependent analgesia with parenteral doses of 5 to 20mg. Dezocine is estimated to be 5 to 9 times more potent than pethidine (meperidine), of similar potency to morphine (although there are minor differences in the time course of analgesia with the 2 agents), and one-fifth as potent as butorphanol. The anaesthetic-sparing effect of dezocine in animals is much greater than that of older agonist-antagonist opioids such as butorphanol and nalbuphine, and approaches that of morphine and fentanyl.

Typical opioid antagonistic activity exhibited by dezocine includes dose-related reversai of morphine-induced loss of righting reflex, body rigidity and respiratory depression. In contrast to nalorphine, dezocine did not induce the jumping response in morphine-treated rodents, but did produce a severe abstinence syndrome in morphine-dependent monkeys.

At therapeutic doses in humans (e.g. 10 mg/70kg), dezocine is a more potent respiratory depressant than morphine during the first hour after administration. However, unlike the dose-dependent respiratory effects of morphine, dezocine-induced respiratory depression reached a ceiling at a dose of approximately 0.30 to 0.40 mg/kg. The ceiling respiratory and analgesic activities of dezocine occurred at the same dosage, and both maximal responses were greater than similar plateau effects previously reported for nalbuphine. The administration of dezocine to morphine-treated volunteers produced an additive analgesic effect, but the respiratory depression associated with the combination given in this order did not exceed that normally associated with dezocine alone.

Dezocine has not been associated with clinically significant haemodynamic changes following administration to patients with postoperative or other pain, or those undergoing diagnostic cardiac catheterisation. Unlike morphine, dezocine did not cause hypotension in the latter group of patients. The limited information available indicates that, as with other agonist/antagonists, the dependence liability of dezocine is likely to be much lower than that of the classic opiates such as morphine. Long term administration of dezocine did not produce addiction in monkeys, but it was equipotent with morphine in producing opiate-like effects, including euphoria, and was consistently identified as ‘dope’ when administered to drug abusers. In this latter regard dezocine differs from other agonist/antagonist drugs such as nalbuphine, pentazocine and cyclazocine, which produce a profile of signs and symptoms readily distinguishable from those of morphine.

Pharmacokinetic Properties

Only very limited data are available concerning the pharmacokinetic disposition of dezocine in humans. Following intravenous administration to healthy male volunteers, dezocine underwent biphasic elimination, with a rapid initial distribution phase. The elimination half-life was approximately 2.5 hours in these subjects. The mean peak serum dezocine concentration of 19 μg/L occurred 35 minutes after a 10mg intramuscular dose in healthy males, while a mean peak concentration of 11 μg/L occurred 1.2 hours after the same dose administered subcutaneously. Animal studies indicate extensive distribution of dezocine, with drug concentrations in highly perfused tissues exceeding that of plasma. The very high systemic clearance of 14C-dezocine in healthy volunteers and animals indicates biliary secretion to be a significant route of elimination of the parent drug and its metabolites.

Therapeutic Trials

Dezocine, usually administered in single intravenous or intramuscular doses, has been compared with the established opioid analgesics morphine, pethidine and butorphanol, and with placebo in patients with moderate to severe pain. The majority of these patients were suffering from postoperative pain, although patients with renal colic and severe cancer pain have also been treated with dezocine. Single doses of dezocine 5 to 15mg produced dose-dependent analgesia in each pain state. The onset and duration of action and magnitude of peak analgesic effect were similar after 10mg doses of dezocine and morphine. However, patient and physician evaluations consistently favoured dezocine. In postoperative pain studies, dezocine was estimated to be 5 to 9 times more potent than pethidine, and approximately one-fifth as potent as butorphanol; once again, at similar analgesic doses patients’ and physicians’ overall impressions usually favoured dezocine over the alternative agent.

In 1 study multiple-dose administration of dezocine for up to 7 days was found to be superior to butorphanol. In contrast to the increasing toxicity of butorphanol, which usually led to its discontinuation, multiple doses of dezocine did not result in either tolerance or limiting adverse effects.

Adverse Effects

Dezocine is at least as well tolerated as morphine, pethidine and butorphanol after single-dose parenteral administration. Overall, the adverse effects of dezocine have been mild, transient events of dose-dependent incidence. The most frequent adverse effects are nausea/vomiting and somnolence, each with a variable incidence of up to 20%. Effects such as dizziness, anxiety, sweating and tachycardia have also been reported, usually at an incidence of less than 5%. In therapeutic doses dezocine does not produce clinically significant respiratory depression. Further information is required to more fully establish the drug’s adverse effect profile during long term use.


In most situations of moderate to severe pain, the effective adult dose of dezocine will be in the range 10 to 15mg, administered intravenously or intramuscularly, repeated 2- to 4-hourly as required. Dezocine has not been evaluated in children, and caution should be observed in patients with renal and especially hepatic dysfunction, and those with compromised respiratory or cardiovascular status.


Morphine Naloxone Respiratory Depression Pethidine Pentazocine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Camu F, Gepts E. Analgesic properties of dezocine for relief of postoperative pain. Acta Anaesthesiologica Belgica 30 (Suppl.): 183–191, 1979PubMedGoogle Scholar
  2. DiFazio CA, Moscicki JC, Magruder MR. Anesthetic potency of nalbuphine and interaction with morphine in rats. Anesthesia and Analgesia 60: 629–633, 1981PubMedCrossRefGoogle Scholar
  3. Downing JW, Brock-Utne JG, Barclay A, Schwegmann IL. WY 16225 (dezocine), a new synthetic opiate agonist-antagonist and potent analgesic: comparison with morphine for relief of pain after lower abdominal surgery. British Journal of Anaesthesia 53: 59–64, 1981PubMedCrossRefGoogle Scholar
  4. Errick JK, Heel RC. Nalbuphine: a preliminary review of its pharmacological properties and therapeutic efficacy. Drugs 26: 191–211, 1983PubMedCrossRefGoogle Scholar
  5. Finucane BT, Floyd JB, Petro DJ. Postoperative pain relief: a double-blind comparison of dezocine, butorphanol, and placebo. Southern Medical Journal 79: 548–552, 1986PubMedCrossRefGoogle Scholar
  6. Fragen RJ, Caldwell N. Comparison of dezocine (WY 16,225) and meperidine as postoperative analgesics. Anesthesia and Analgesia 57: 563–566, 1978PubMedGoogle Scholar
  7. Freed ME, Potoski JR, Freed GH, Conklin GL, Bell SC. Analgesic agents. 3. New bridged aminotetralins. Journal of Medicinal Chemistry 19: 476–480, 1976PubMedCrossRefGoogle Scholar
  8. Freed ME, Potoski JR, Freed EH, Conklin GL, Malis JL. Bridged aminotetralins as novel potent analgesic substances. Journal of Medicinal Chemistry 16: 595–599, 1973PubMedCrossRefGoogle Scholar
  9. Gal TJ, DiFazio CA. Ventilatory and analgesic effects of dezocine in humans. Anesthesiology 61: 716–722, 1984PubMedCrossRefGoogle Scholar
  10. Galloway FM, Varma S. Double-blind comparison of intravenous doses of dezocine, butorphanol and placebo for relief of postoperative pain. Anesthesia and Analgesia 65: 283–287, 1986PubMedGoogle Scholar
  11. Gilbert PE, Martin WR. The effects of morphine- and nalorphine-like drugs in the nondependent morphine-dependent and cyclazocine-dependent chronic spinal dog. Journal of Pharmacology and Experimental Therapeutics 198: 66–82, 1976PubMedGoogle Scholar
  12. Gravenstein JS. Dezocine for postoperative wound pain. International Journal of Clinical Pharmacology, Therapy and Toxicology 22: 502–505, 1984Google Scholar
  13. Hall RI, Murphy MR, Szlam F, Hug Jr CC. Dezocine-MAC reduction and evidence for myocardial depression in the presence of enflurane. Anesthesia and Analgesia 66: 1169–1174, 1987PubMedGoogle Scholar
  14. Hoffman JC, DiFazio CA. The anaesthesia sparing effect of pentazocine, meperidine and morphine. Archives Internationales de Pharmacodynamie et de Thérapie 186: 261–268, 1970PubMedGoogle Scholar
  15. Holmes B, Ward A. Meptazinol: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy. Drugs 30: 285–312, 1985PubMedCrossRefGoogle Scholar
  16. Holtzman SG. Drug discrimination studies. Drug and Alcohol Dependence 14: 263–282, 1985PubMedCrossRefGoogle Scholar
  17. Houde RW. Analgesic effectiveness of the narcotic agonist-antagonists. British Journal of Clinical Pharmacology 7: 2975–3085, 1979CrossRefGoogle Scholar
  18. Hoyumpa A, Snowdy P, Nichols S, Johnson R, Stump D. Effect of cirrhosis on the disposition of dezocine. Abstract. Clinical Pharmacology and Therapeutics 41: 226, 1987Google Scholar
  19. Jasinski DR. Assessment of the abuse potential of morphine-like drugs (methods used in man). In Martin WR (Ed.) Handbook of Experimental Pharmacology, Vol. 45, pp. 197–258, Springer-Verlag, Heidelberg, 1977Google Scholar
  20. Jasinski DR. Human pharmacology of narcotic antagonists. British Journal of Pharmacology 7 (Suppl.): 287S–290S, 1979CrossRefGoogle Scholar
  21. Jasinski DR, Preston KL. Assessment of dezocine for morphine-like subjective effects and miosis. Clinical Pharmacology and Therapeutics 38: 544–548, 1985PubMedCrossRefGoogle Scholar
  22. Keats AS. The effect of drugs on respiration in man. Annual Review of Pharmacology and Toxicology 25: 41–65, 1985PubMedCrossRefGoogle Scholar
  23. Kosterlitz HW, Lord JAH, Watt AJ. Morphine receptor in the myenteric plexus of the guinea pig ileum. In Kosterlitz HW, et al. (Eds) Agonist and antagonist actions of narcotic analgesic drugs, pp. 45–61, University Park Press, Baltimore, 1973Google Scholar
  24. Lewis AJ, Kirchner T. A comparison of the cardiorespiratory effects of cinamadol, dezocine, morphine and pentazocine in the anaesthetised dog. Archives Internationales de Pharmacodynamie et de Thérapie 250: 73–83, 1981PubMedGoogle Scholar
  25. Locniskar A, Greenblatt DJ, Zinny MA. Pharmacokinetics of dezocine, a new analgesic: effect of dose and route of administration. European Journal of Clinical Pharmacology 30: 121–123, 1986PubMedCrossRefGoogle Scholar
  26. Malis JL, Rosenthale ME, Gluckman MI. Animal pharmacology of Wy-16,225, a new analgesic agent. Journal of Pharmacology and Experimental Therapeutics 194: 488–498, 1975PubMedGoogle Scholar
  27. Martin WR. History and development of mixed opioid agonists, partial agonists and antagonists. British Journal of Clinical Pharmacology 7: 2735–2795, 1979CrossRefGoogle Scholar
  28. Martin WR, Eades CG, Thompson JA, Huppier RE, Gilbert PE. The effects of morphine- and nalorphine-like drugs in the non-dependent and morphine-dependent chronic spinal dog. Journal of Pharmacology and Experimental Therapeutics 197: 517–532, 1976PubMedGoogle Scholar
  29. Murphy MR, Hug Jr CC. The enflurane sparing effect of morphine, butorphanol and nalbuphine. Anesthesiology 57: 489–492, 1982aPubMedCrossRefGoogle Scholar
  30. Murphy MR, Hug Jr CC. The anesthetic potency of fentanyl in terms of its reduction of enflurane MAC. Anesthesiology 57: 485–488, 1982bPubMedCrossRefGoogle Scholar
  31. Oosterlinck W, Verbaeys A. Preliminary clinical experience with dezocine, a new potent analgesic. Current Medical Research and Opinion 6: 472–474, 1980PubMedCrossRefGoogle Scholar
  32. Pandit UA, Kothary SP, Pandit SK. Intravenous dezocine for postoperative pain: a double-blind, placebo-controlled comparison with morphine. Journal of Clinical Pharmacology 26: 275–280, 1986PubMedGoogle Scholar
  33. Pandit SK, Kothary SP, Pandit UA, Kunz NR. Double-blind placebo-controlled comparison of dezocine and morphine for postoperative pain relief. Canadian Anaesthetists’ Society Journal 32: 583–591, 1985PubMedCrossRefGoogle Scholar
  34. Romagnoli A, Keats AS. Ceiling respiratory depression by dezocine. Clinical Pharmacology and Therapeutics 35: 367–373, 1984PubMedCrossRefGoogle Scholar
  35. Rothbard RL, Schreiner BF, Yu PN. Hemodynamic and respiratory effects of dezocine, ciramadol and morphine. Clinical Pharmacology and Therapeutics 38: 84–88, 1985PubMedCrossRefGoogle Scholar
  36. Rowlingson JC, Moscicki JC, DiFazio CA. Anesthetic potency of dezocine and its interaction with morphine in rats. Anesthesia and Analgesia 62: 899–902, 1983PubMedCrossRefGoogle Scholar
  37. Schaefer GJ, Holtzman SG. Morphine-like stimulus effects in the monkey: opioids with antagonist properties. Pharmacology, Biochemistry and Behaviour 14: 241–245, 1981CrossRefGoogle Scholar
  38. Sisenwine SF, Tio CO. The metabolic disposition of dezocine in rhesus monkeys and female rats given 14C-dezocine intragastrically. Drug Metabolism and Disposition 9: 37–42, 1981PubMedGoogle Scholar
  39. Sisenwine SF, Tio CO, Liu AL, Ruelius HW. Pharmacokinetics of parenteral dezocine in rhesus monkeys and dogs. Drug Metabolism and Disposition 10: 366–370, 1982PubMedGoogle Scholar
  40. Stambaugh Jr JE, McAdams J. Comparison of intramuscular dezocine with butorphanol and placebo in chronic cancer pain: a method to evaluate analgesia after both single and repeated doses. Clinical Pharmacology and Therapeutics 42: 210–219, 1987PubMedCrossRefGoogle Scholar
  41. Staquet M. A double-blind study of dezocine in cancer pain. Journal of Clinical Pharmacology 19: 392–394, 1979PubMedGoogle Scholar
  42. Vinik HR, McFarland L, Wright D, Baker W. Double-blind postoperative study comparing multiple doses of dezocine (WY 16225) with morphine and placebo. Abstract. Anesthesiology 57: A189, 1982CrossRefGoogle Scholar
  43. Warren MM, Boyce WH, Evans JW, Peters PC. A double-blind comparison of dezocine and morphine in patients with acute renal and ureteral colic. Journal of Urology 134: 457–459, 1985PubMedGoogle Scholar
  44. WHO Technical Report Series 775, Geneva, 1989. Woods JH. Narcotic-reinforced responding: a rapid screening procedure. Proceedings of the 39th Meeting of the Committee on Problems of Drug Dependence, Cambridge, Massachusetts, pp. 420–449, 1977Google Scholar
  45. Woods JH, Young AM, Herling S. Classification of narcotics on the basis of their reinforcing, discriminative, and antagonist effect in rhesus monkeys. Federation Proceedings 41: 221–227, 1982PubMedGoogle Scholar
  46. Wuest HP, Bellville JW. The respiratory effect of dezocine and pentazocine in man. Journal of Clinical Pharmacology 19: 205–210, 1979PubMedGoogle Scholar
  47. Young AM, Stephens KR, Hein DW, Woods JH. Reinforcing and discriminative stimulus properties of mixed agonist-antagonist opioids. Journal of Pharmacology and Experimental Therapeutics 229: 118–126, 1984PubMedGoogle Scholar

Copyright information

© ADIS Press Limited 1989

Authors and Affiliations

  • John J. O’Brien
    • 1
  • Paul Benfield
    • 1
  1. 1.Adis Drug Information ServicesAucklandNew Zealand

Personalised recommendations