Skip to main content
NCBI home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1988 Jul;26(1):79–87. doi: 10.1111/j.1365-2125.1988.tb03367.x

Psychomotor, respiratory and neuroendocrinological effects of nalbuphine and haloperidol, alone and in combination, in healthy subjects.

U Saarialho-Kere 1
PMCID: PMC1386503  PMID: 3060191

Abstract

1. Actions and interactions on performance and respiration of single intramuscular doses of 0.15 mg kg-1 nalbuphine and oral haloperidol twice daily for 2 days were studied double-blind and cross-over in 12 healthy volunteers. 2. Objective measurements of performance (choice reaction, tracking, attention, flicker fusion, Maddox wing, digit symbol substitution) and respiratory function (minute volume, end-tidal carbon dioxide), and subjective assessments on visual analogue scales were done at baseline and 1 h, 2.5 h and 4 h after the injection of nalbuphine. Plasma concentrations of nalbuphine were estimated by radioreceptor ([3H]-dihydromorphine) assay, and those of prolactin and growth hormone by radioimmunoassay. 3. Nalbuphine affected digit substitution, reaction time, extraocular muscle balance and flicker recognition, and depressed respiration most clearly 1 and 2.5 h post injection. Motor skills were impaired only briefly. Haloperidol alone proved inert on performance but enhanced the decremental effects of nalbuphine on digit substitution and exophoria at 1 h. It did not interact with nalbuphine on the ventilatory function. 4. Plasma concentrations of nalbuphine expressed as morphine equivalents ranged from 5 to 52 ng ml-1, indicating considerable mu-opiate affinity. Treatment with haloperidol increased plasma prolactin moderately whilst nalbuphine raised it markedly 1 and 2.5 h post injection. Nalbuphine elevated plasma growth hormone at 1 h post injection only.

Full text

PDF
79

Selected References

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

  1. Berkowitz B. A. The relationship of pharmacokinetics to pharmacological activity: morphine, methadone and naloxone. Clin Pharmacokinet. 1976;1(3):219–230. doi: 10.2165/00003088-197601030-00004. [DOI] [PubMed] [Google Scholar]
  2. Budd K. Psychotropic drugs in the treatment of chronic pain. Anaesthesia. 1978 Jun;33(6):531–534. doi: 10.1111/j.1365-2044.1978.tb08391.x. [DOI] [PubMed] [Google Scholar]
  3. Delitala G., Grossman A., Besser M. Differential effects of opiate peptides and alkaloids on anterior pituitary hormone secretion. Neuroendocrinology. 1983 Oct;37(4):275–279. doi: 10.1159/000123558. [DOI] [PubMed] [Google Scholar]
  4. Downes C. P., Lewis P. E., Stone M. A. A comparison of the binding of sigma opioids and phencyclidine, and the interaction with antipsychotic drugs in rat brain membranes. Br J Pharmacol. 1986 May;88(1):231–237. doi: 10.1111/j.1476-5381.1986.tb09491.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Errick J. K., Heel R. C. Nalbuphine. A preliminary review of its pharmacological properties and therapeutic efficacy. Drugs. 1983 Sep;26(3):191–211. doi: 10.2165/00003495-198326030-00002. [DOI] [PubMed] [Google Scholar]
  6. Gal T. J., DiFazio C. A., Moscicki J. Analgesic and respiratory depressant activity of nalbuphine: a comparison with morphine. Anesthesiology. 1982 Nov;57(5):367–374. doi: 10.1097/00000542-198211000-00004. [DOI] [PubMed] [Google Scholar]
  7. Harper M. H., Hickey R. F., Cromwell T. H., Linwood S. The magnitude and duration of respiratory depression produced by fentanyl and fentanyl plus droperidol in man. J Pharmacol Exp Ther. 1976 Nov;199(2):464–468. [PubMed] [Google Scholar]
  8. Jordan C. Assessment of the effects of drugs on respiration. Br J Anaesth. 1982 Jul;54(7):763–782. doi: 10.1093/bja/54.7.763. [DOI] [PubMed] [Google Scholar]
  9. Kamata K., Ogawa K., Kameyama T. Modification of antinociceptive action of morphine by dopamine agonist and antagonist in mice. Jpn J Pharmacol. 1985 May;38(1):113–115. doi: 10.1254/jjp.38.113. [DOI] [PubMed] [Google Scholar]
  10. Keats A. S. The effect of drugs on respiration in man. Annu Rev Pharmacol Toxicol. 1985;25:41–65. doi: 10.1146/annurev.pa.25.040185.000353. [DOI] [PubMed] [Google Scholar]
  11. Kocher R. Use of psychotropic drugs for the treatment of chronic severe pains. Int Rehabil Med. 1979;1(3):116–120. doi: 10.3109/03790797909163938. [DOI] [PubMed] [Google Scholar]
  12. Lal H. Narcotic dependence, narcotic action and dopamine receptors. Life Sci. 1975 Aug 15;17(4):483–495. doi: 10.1016/0024-3205(75)90081-8. [DOI] [PubMed] [Google Scholar]
  13. Linnavuo M., Yliläkkölä P., Mattila M. J., Mäki M., Seppälä T. A new device to measure drug-induced changes on reactive and coordinative skills of human performance. Pharmacol Toxicol. 1987 Aug;61(2):142–147. doi: 10.1111/j.1600-0773.1987.tb01792.x. [DOI] [PubMed] [Google Scholar]
  14. Linnoila M. Drug effects on psychomotor skills related to driving: interaction of atropine, glycopyrrhonium and alcohol. Eur J Clin Pharmacol. 1973 Aug;6(2):107–112. doi: 10.1007/BF00562436. [DOI] [PubMed] [Google Scholar]
  15. Lo M. W., Lee F. H., Schary W. L., Whitney C. C., Jr The pharmacokinetics of intravenous, intramuscular, and subcutaneous nalbuphine in healthy subjects. Eur J Clin Pharmacol. 1987;33(3):297–301. doi: 10.1007/BF00637566. [DOI] [PubMed] [Google Scholar]
  16. MOORE J., DUNDEE J. W. Alterations in response to somatic pain associated with anaesthesia. VII. The effects of nine phenothiazine derivatives. Br J Anaesth. 1961 Sep;33:422–431. doi: 10.1093/bja/33.9.422. [DOI] [PubMed] [Google Scholar]
  17. McGilliard K. L., Takemori A. E. The effect of dopaminergic modifiers on morphine-induced analgesia and respiratory depression. Eur J Pharmacol. 1979 Feb 15;54(1-2):61–68. doi: 10.1016/0014-2999(79)90408-4. [DOI] [PubMed] [Google Scholar]
  18. Müller E. E., Locatelli V., Cella S., Peñalva A., Novelli A., Cocchi D. Prolactin-lowering and -releasing drugs. Mechanisms of action and therapeutic applications. Drugs. 1983 Apr;25(4):399–432. doi: 10.2165/00003495-198325040-00004. [DOI] [PubMed] [Google Scholar]
  19. Petts H. V., Pleuvry B. J. Interactions of morphine and methotrimeprazine in mouse and man with respect to analgesia, respiration and sedation. Br J Anaesth. 1983 May;55(5):437–441. doi: 10.1093/bja/55.5.437. [DOI] [PubMed] [Google Scholar]
  20. Pfeiffer A., Braun S., Mann K., Meyer H. D., Brantl V. Anterior pituitary hormone responses to a kappa-opioid agonist in man. J Clin Endocrinol Metab. 1986 Jan;62(1):181–185. doi: 10.1210/jcem-62-1-181. [DOI] [PubMed] [Google Scholar]
  21. Read D. J. A clinical method for assessing the ventilatory response to carbon dioxide. Australas Ann Med. 1967 Feb;16(1):20–32. doi: 10.1111/imj.1967.16.1.20. [DOI] [PubMed] [Google Scholar]
  22. Rolandi E., Franceschini R., Marabini A., Messina V., Barreca T. Serum concentrations of PRL, GH, LH, FSH, TSH and cortisol after single administration to man of a new synthetic narcotic analgesic butorphanol. Eur J Clin Pharmacol. 1984;26(5):563–565. doi: 10.1007/BF00543485. [DOI] [PubMed] [Google Scholar]
  23. Saarialho-Kere U., Mattila M. J., Paloheimo M., Seppälä T. Psychomotor, respiratory and neuroendocrinological effects of buprenorphine and amitriptyline in healthy volunteers. Eur J Clin Pharmacol. 1987;33(2):139–146. doi: 10.1007/BF00544557. [DOI] [PubMed] [Google Scholar]
  24. Saarialho-Kere U., Mattila M. J., Seppälä T. Pentazocine and codeine: effects on human performance and mood and interactions with diazepam. Med Biol. 1986;64(5):293–299. [PubMed] [Google Scholar]
  25. Schmidt W. K., Tam S. W., Shotzberger G. S., Smith D. H., Jr, Clark R., Vernier V. G. Nalbuphine. Drug Alcohol Depend. 1985 Feb;14(3-4):339–362. doi: 10.1016/0376-8716(85)90066-3. [DOI] [PubMed] [Google Scholar]
  26. Seppala T., Linnoila M., Mattila M. J. Drugs, alcohol and driving. Drugs. 1979 May;17(5):389–408. doi: 10.2165/00003495-197917050-00008. [DOI] [PubMed] [Google Scholar]
  27. Tandon M. K. Effect on respiration of diazepam, chloropromazine and haloperidol in patients with chronic airways obstruction. Aust N Z J Med. 1976 Dec;6(6):561–565. doi: 10.1111/j.1445-5994.1976.tb03995.x. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES