General Principles and Methods of Evaluation of Neuromuscular Blocking Agents in Anesthesiology

  • F. F. Foldes
  • H. Nagashima
  • D. Duncalf
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 79)


There is considerable species variation in the pharmacodynamic effects (Paton and Zaimis 1949; Foldes 1954) and pharmacokinetics (Agostin 1976) of neuromuscular (NM) blocking agents (NMBA). Because of this, the information obtained in animal experiments on the potency, onset, and duration of the NM effect of NMBA and on their side effect liability and disposition has only limited relevance to the effects of these compounds in humans. Thus, for example, pancuronium (Pavulon) is about five and ten times more potent than tubocurarine (Tc) in humans (Baird and Reid 1967) and cats (buckett et al. 1968), respectively, but about five times less potent than Tc in rats (Chaudhry and Foldes 1981). Vecuronium (Org-NC-45, Norcuron) is more potent than pancuronium in humans (Crul and Booij 1980) and dogs (Marshall et al. 1980), but less potent than pancuronium in rats, cats, and rhesus monkeys (Marshall et al. 1980). To predict the effects of NMBA in the clinical setting, it is necessary to investigate their pharmacodynamics and pharmacokinetics, with accepted pharmacologic methods, in humans. Preliminary observations should be carried out in conscious human subjects. These should be followed by more comprehensive studies in anesthetized volunteers and/or patients.


Grip Strength Fractional Dose Neuromuscular Blocking Agent Inhalation Anesthetic Neuromuscular Blocking Drug 
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  1. Agoston S (1976) Disposition and effects of some non-depolarizing neuromuscular blocking agents in animal and man. Doctoral thesis, University of Groningen, VRB GroningenGoogle Scholar
  2. Agoston S, Crul JF, Kersten UW, Scaf AHJ (1977) Relationship of the serum concentration of pancuronium to its neuromuscular activity in man. Anesthesiology 47:509–512PubMedCrossRefGoogle Scholar
  3. Agoston S, Salt P, Newton D, Bencini A, Boomsma P, Erdmann W (1980) The neuromuscular blocking action of ORG-NC45, a new pancuronium derivative in anaesthetized patients. Br J Anaesth 52:53S–59SPubMedCrossRefGoogle Scholar
  4. Alam M, Anrep CV, Barsoum GS, Taloat M, Weininger E (1939) Liberation of histamine from the skeletal muscles by curare. J Physiol (Lond) 95:148–158Google Scholar
  5. Ali HH, Utting JE, Gray TC (1973) Quantitative assessment of residual antidepolarizing block (Part 1). Br J Anaesth 43:473–485CrossRefGoogle Scholar
  6. Ali HH, Wilson RS, Savarese JJ, Kitz RJ (1975) The effect of tubocurarine on indirectly elicited train-of-four muscle response and respiratory measurements in humans. Br J Anaesth 47:570–574PubMedCrossRefGoogle Scholar
  7. Auer J, Meltzer SJ (1914) The effect of ether inhalation upon the skeletal motor mechanism. J Pharmacol Exp Ther 5:521–522Google Scholar
  8. Baird WLM, Reid AM (1967) The neuromuscular properties of a new steroid compound, pancuronium bromide. Br J Anaesth 39:775–780PubMedCrossRefGoogle Scholar
  9. Baraka A (1964) The influence of carbon dioxide on the neuromuscular block caused by tubocurarine chloride in the human subject. Br J Anaesth 36:272–278PubMedCrossRefGoogle Scholar
  10. Bowman WC (1980) Pharmacology of neuromuscular function. University Park, Baltimore, pp 99–115Google Scholar
  11. Buckett WR, Narjoribanks CEB, Marwick FA, Morton MB (1968) The pharmacology of pancuronium bromide (Org. NA97), a new potent steroidal neuromuscular blocking agent. Br J Pharmacol 32:671–682Google Scholar
  12. Burkett L, Bikhazi GB, Thomas KC Jr, Rosenthal DA, Wirta MG, Foldes FF (1979) Mutual potentiation of the neuromuscular effects of antibiotics and relaxants. Anesth Analg 58:107–115PubMedCrossRefGoogle Scholar
  13. Cannard TH, Zaimis E (1959) The effect of lowered muscle temperature on the action of neuromuscular blocking drugs in man. J Physiol 149:112–119PubMedGoogle Scholar
  14. Chaudhry I, Foldes FF (1981) In vitro effect of three new neuromuscular blocking agents. Anesthesiology 55:A220Google Scholar
  15. Chaudhry I, Ohta Y, Nagashima H, Deery A, Foldes FF (1980) Inhalation anesthetic relaxant interactions in vitro. Anesthesiology 53:S266CrossRefGoogle Scholar
  16. Churchill-Davidson HC, Richardson AT (1952) Decamethonium iodide (C10): Some observations on its action using electromyography. Proc R Soc Med 45:179–185PubMedGoogle Scholar
  17. Collier HOJ, Macauley B (1952) The pharmacological properties of “Laudolissin” — A long-acting curarizing agent. Br J Pharmacol 7:398–408Google Scholar
  18. Crul JF, Booij LHD (1980) First clinical experience with ORG-NC45. Br J Anaesth 52:49S–52SPubMedCrossRefGoogle Scholar
  19. Davis N, Karp M (1951) Dosage guide for administration of halogen salts of d-tubocurarine dimethyl ether. Anesth Analg 30:47–51CrossRefGoogle Scholar
  20. Deery A, Foldes FF, Benad G, McCloskey MA (1982) Interaction of neuromuscular blocking agents with human Cholinesterase. Anesthesiology 56:A275.CrossRefGoogle Scholar
  21. Donlon JV Jr, Savarese JJ, Ali HH, Teplik RS (1980) Human dose-response curves for neuromuscular blocking drugs. Anesthesiology 53:161–166PubMedCrossRefGoogle Scholar
  22. Foldes FF (1951) The use of mytolon chloride in anesthesiology. Ann NY Acad Sci 54:503–511PubMedCrossRefGoogle Scholar
  23. Foldes FF (1954) The mode of action of quaternary ammonium type neuromuscular blocking agents. Br J Anaesth 26:394–398PubMedCrossRefGoogle Scholar
  24. Foldes FF (1959) Factors which alter the effects of muscle relaxants. Anesthesiology 20:464–504PubMedCrossRefGoogle Scholar
  25. Foldes FF (1960) The pharmacology of neuromuscular blocking agents in man. Clin Pharmacol Ther 1:345–395PubMedGoogle Scholar
  26. Foldes FF (1966) The choice and mode of administration of relaxants. In: Foldes FF (ed) Muscle relaxants. Davis, Philadephia, pp 4–5Google Scholar
  27. Foldes FF (1978) Enzymes of acetylcholine metabolism. In: Foldes FF (ed) Enzymes in anesthesiology. Springer, New York Heidelberg Berlin, p 124CrossRefGoogle Scholar
  28. Foldes FF (1981) Circulatory effects of neuromuscular blocking agents. Proceedings of the 10th International Anaesthesia Postgraduate Course, June 29 to July 3, Vienna, Austria. Egermann, Vienna, pp 71–78Google Scholar
  29. Foldes FF, Foldes VM (1965) ω-amino fatty acid esters of choline. Interaction with cholinesterases and neuromuscular activity in man. J Pharmacol Exp Ther 150:220–230PubMedGoogle Scholar
  30. Foldes FF, Wnuck AL, Hodges RJ, Thesleff S, deBeer EJ (1957) The mode of action of depolarizing relaxants. Anesth Analg 36:23–37PubMedCrossRefGoogle Scholar
  31. Foldes FF, Monte AP, Brunn HM Jr, Wolfson B (1961) Studies with muscle relaxants in unanesthetized subjects. Anesthesiology 22:230–236PubMedCrossRefGoogle Scholar
  32. Foldes FF, Foldes VM, Smith JC, Zsigmond EK (1963) The relation between plasma Cholinesterase and prolonged apnea caused by succinylcholine. Anesthesiology 24:208–216PubMedCrossRefGoogle Scholar
  33. Foldes FF, Kuze S, Vizi ES, Deery A (1978) The influence of temperature on neuromuscular performance. J Neural Transm 43:27–45PubMedCrossRefGoogle Scholar
  34. Foldes FF, Bencini A, Newton D (1980) Influence of halothane and enflurane on the neuromuscular effects of ORG-NC45 in man. Br J Anaesth 52:64S–65SPubMedGoogle Scholar
  35. Foldes FF, Yun H, Radnay PA, Badola RP, Kaplan R, Nagashima H (1981) Antagonism of the NM effect of ORG-NC45 by edrophonium. Anesthesiology 55:A201Google Scholar
  36. Foldes FF, Deery A, Benad G, McCloskey MA, Strauch R (1982) The binding of neuromuscular blocking agents to plasma proteins. Anesthesiology 56:A274CrossRefGoogle Scholar
  37. Foldes FF, Nagashima H, Boros M, Tassonyi E, Fitzal S, Agoston S (1983) Muscular relaxation with atracurium, vecuronium and Duador under balanced anaesthesia. Br J Anaesth 55:97S–103SPubMedCrossRefGoogle Scholar
  38. Greenblatt DJ, Koch-Weser J (1975) Clinical pharmacokinetics. N Engl J Med 293:702–705PubMedCrossRefGoogle Scholar
  39. Grob D, Lilienthal JL, Harvey AM (1947) On certain vascular effects of curare in man: the “histamine” reaction. Bull Johns Hopkins Hosp 80:299–322PubMedGoogle Scholar
  40. Gubner RS (1961) Simple arthropometric indices of body fatness and heart size. Clin Res 9:15Google Scholar
  41. Ham J, Miller RD, Benet LZ, Matteo RS, Roderick LL (1978) The effect of temperature on the pharmacokinetics and pharmacodynamics of d-tubocurarine. Anesthesiology 49:324–328PubMedCrossRefGoogle Scholar
  42. Hoppe JO (1955) Observations on the potency of neuromuscular blocking agents with particular reference to succinylcholine. Anesthesiology 16:91–124PubMedCrossRefGoogle Scholar
  43. Kersten UW, Meijer DKF, Agoston S (1973) Fluorimetric and chromatographic determination of pancuronium bromide and its metabolites in biological materials. Clin Chim Acta 44:59–66PubMedCrossRefGoogle Scholar
  44. Landmesser CN (1947) A study of the bronchoconstrictor and hypotensive actions of curarizing drugs. Anesthesiology 8:506–523PubMedCrossRefGoogle Scholar
  45. Lippold OCJ (1952) Relation between integrated action potentials in human muscle and its isometric tension. J Physiol 117:492–499PubMedGoogle Scholar
  46. Maclagen J (1976) Competitive neuromuscular blocking drugs. In: Zaimis E (ed) Neuromuscular junction. Handbook of experimental pharmacology, vol 42. Springer, Berlin Heidelberg New York, pp 421–486Google Scholar
  47. Marshall IG, Agoston S, Booij LHDJ, Durant NN, Foldes FF (1980) Pharmacology of ORG-NC45 compared with other non-depolarizing neuromuscular blocking drugs. Br J Anaesth 52:11S–19SPubMedCrossRefGoogle Scholar
  48. Matteo RS, Spector S, Horowitz P (1974) Relation of serum d-tubocurarine concentration to neuromuscular blockade in man. Anesthesiology 41:440–443PubMedCrossRefGoogle Scholar
  49. Miller RD (1975) Factors affecting the action of muscle relaxants. In: Katz RL (ed) Muscle relaxants, Monographs in anaesthesiology, no 3. Excerpta Medica, Amsterdam, pp 163–192Google Scholar
  50. Miller RD, Eger EI II, Way WL (1971) Comparative neuromuscular effects of forane and halothane alone and in combination with d-tubocurarine in man. Anesthesiology 35:38–42PubMedCrossRefGoogle Scholar
  51. Miller RD, Agoston S, van der Pol F, Booij LHDJ, Crul JF, Ham J (1978) Hypothermia and the pharmacokinetics and pharmacodynamics of pancuronium in the cat. J Pharmacol Exp Ther 207:532–538PubMedGoogle Scholar
  52. Nagashima H, Yun H, Radnay PA, Duncalf D, Kaplan R, Foldes FF (1981) Influence of anesthesia on human dose-response of ORG-NC45. Anesthesiology 55:A202Google Scholar
  53. Nguyen HD, Nagashima H, Kaplan R, Lauber R, Yun H, Foldes FF (1982) Relaxation with BW33A under neurolept and enflurane anesthesia. Anesthesiology 57:A277CrossRefGoogle Scholar
  54. Norman J, Katz RL, Seed RF (1970) The neuromuscular blocking action of pancuronium in man during anesthesia. Br J Anaesth 42:702–710PubMedCrossRefGoogle Scholar
  55. Ohta Y, Nagashima H, Lofrumento R, Foldes FF (1980) Halothane-isoflurane relaxant interactions in vivo. Anesthesiology 53:S265CrossRefGoogle Scholar
  56. Osserman KE (1958) Myasthemia Gravis. Grune and Stratton, New York, pp 100–101Google Scholar
  57. Paton WDM, Zaimis EJ (1949) The pharmacological actions of polymethylene bistrimethylammonium salts. Br J Pharmacol 4:381–400Google Scholar
  58. Payne JP (1958) The influence of carbon dioxide on the neuromuscular blocking activity of relaxant drugs in the cat. Br J Anaesth 30:206–216PubMedCrossRefGoogle Scholar
  59. Pelikan EW, Tether JE, Unna KR (1953) Sensitivity of myasthenia gravis patients to d-tubocurarine and decamethonium. Neurology 3:284–296PubMedGoogle Scholar
  60. Poppers PJ, Finster M (1975) The use of muscle relaxants in obstetrics. In: Katz RL (ed) Muscle relaxants, Monographs in anesthesiology no 3. Excerptia Medica, Amsterdam, pp 205–208Google Scholar
  61. Riker WF, Wescoe WC (1951) The pharmacology of flaxedil with observations on certain analogs. Ann NY Acad Sci 54:373–392PubMedCrossRefGoogle Scholar
  62. Shore PA, Burkhalter A, Cohn VH (1959) A method for the fluorometric assay of histamine in tissues. J Pharmacol Exp Ther 127:182–186PubMedGoogle Scholar
  63. Thomas ET (1957) The effect of tubocurarine chloride on the blood pressure of anaesthetized patients. Lancet 2:772–773CrossRefGoogle Scholar
  64. Unna KR, Pelikan EW (1951) Evaluation of curarizing drugs in man. VI. Critique of experiments on unanesthetized subjects. Ann NY Acad Sci 54:480–492PubMedCrossRefGoogle Scholar
  65. Van Rossum JN (1971) Significance of pharmacokinetics for drug design. In: Ariens EJ (ed) Drug design, vol 1. Academic, New York, pp 495–503Google Scholar
  66. Waud BE (1975) Serum d-tubocurarine concentration and twitch height. Anesthesiology 43:381–382PubMedCrossRefGoogle Scholar
  67. Wulfsohn NL (1972) Ketamine dosage for induction based on lean body mass. Anesth Analg 51:299–305PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1986

Authors and Affiliations

  • F. F. Foldes
  • H. Nagashima
  • D. Duncalf

There are no affiliations available

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