Skip to main content

Advertisement

Log in

The pre- and postjunctional components of the neuromuscular effect of antibiotics

  • Original Articles
  • Published:
Journal of Anesthesia Aims and scope Submit manuscript

Abstract

The relative contributions of the pre- and postsynaptic components of the myoneural blocking effect of different antibiotics were studied using: (a) a radioactive method that measures selectively the Ca2+-dependent, stimulation evoked, quantally released,3H-acetylcholine (3H-ACh) from the mousein vitro phrenic nerve-hemidiaphragm preparation without cholinesterase inhibition; (b) measurement of the force of contraction of the indirectly or directly stimulated muscle. The antibiotics studied (neomycin, polymyxin B and lincomycin), reduced the release of3H-ACh evoked by stimulation (18 trains of 40 shocks at 50 Hz) in a concentration dependent manner. While the inhibitory effect of neomycin was inversely related to [Ca2+] o , that of lincomycin was moderately and that of polymyxin B was not affected by increasing [Ca2+] o from 0.75 to 5.0 mM. Similarly, the dtubocurarine (d-Tc) -induced inhibition of the release of3H-ACh was independent of [Ca2+] o . The K-channel blocking agent, 4-aminopyridine (4-AP), enhanced the release of ACh in a concentration dependent manner and prevented the neuromuscular effect of neomycin. However, the neuromuscular effect of polymyxin B and of lincomycin was not affected by 4-AP. Atropine, enhanced the release of3H-ACh. Antibiotics, however, were still able to reduce the release of ACh when the negative muscarinic feedback mechanism of ACh release was eliminated by atropine. Our findings indicate that the antibiotics studied possess both pre — and postsynaptic effects. Presynaptically they reduce the evoked release of ACh; postsynaptically they inhibit muscle contractility. The rank order of presynaptic action is neomycin >polymyxin B >lincomycin.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Timmerman JC, Long JP, Pittinger CB: Neuromuscular blocking properties of various antibiotic agents. Toxicol Appl Pharmacol 1:299–304, 1959

    Article  CAS  Google Scholar 

  2. Caputy AJ, Kim YI, Sanders DB: The neuromuscular blocking effects of therapeutic concentrations of various antibiotics on normal rat skeletal muscle: A quantitative comparison. J Pharmacol Exp Ther 217:369–378, 1981

    CAS  PubMed  Google Scholar 

  3. Lüllman H, Reuter H: Über die Hemmung der neuromuskularen Übertragung durch einige Antibiotika. Chemotherapia 1:375–383, 1960

    Article  Google Scholar 

  4. Burkett L, Bikhazi GB, Thomas KC, Rosenthal DA, Wirta MG, Foldes FF: Mutual potentiation of the neuromuscular effects of antibiotics and relaxants. Anesth Analg 58:107–115,1979

    Article  CAS  PubMed  Google Scholar 

  5. Foldes FF, Foldes VM, Benz HG: Prolonged respiratory depression caused by drug combinations. JAMA 183:672–677, 1963

    CAS  PubMed  Google Scholar 

  6. Pittinger CB, Eryasa Y, Adamson R: Antibiotic-induced paralysis. Anesth Analg 49:487–501, 1970

    CAS  PubMed  Google Scholar 

  7. Pittinger C, Adamson R: Antibiotic blockade of neuromuscular function. Ann Rev Pharmacol 12:169–184, 1972

    Article  CAS  PubMed  Google Scholar 

  8. Miller RD: Factors affecting the action of muscle relaxants. In: Muscle Relaxants. Edited by RL Katz. Amsterdam, Excerpta Medica, pp. 163–191, 1975

    Google Scholar 

  9. Bowman WC: Pharmacology of Neuromuscular Function. John Wright & Sons Ltd, Bristol. 1980

    Google Scholar 

  10. Wright JM, Collier B: The effects of neomycin upon transmitter release and action. J Pharmacol Exp Ther 200:576–587, 1997

    Google Scholar 

  11. Dretchen KL, Gergis SD, Sokol MD, Long JP: Effect of various antibiotics on neuromuscular transmission. Eur J Pharmac 18:201–203, 1972

    Article  CAS  Google Scholar 

  12. Szerb JC, Somogyi GT: Depression of acetylcholine release from cerebral cortical slices by cholinesterase inhibition and by oxotremorine. Nature (Lond) 241:121–122, 1973

    CAS  Google Scholar 

  13. Elmquist D, Josefsson JO: The nature of neuromuscular block produced by neomycin. Acta Physiol Scand 54:105–110, 1962

    Article  Google Scholar 

  14. Prado WA, Corrado AP, Marseillan RF: Competitive antagonism between calcium and antibiotics at the neuromuscular junction. Arch Int Pharmacodyn Ther 231:297–307, 1978

    CAS  PubMed  Google Scholar 

  15. Singh YN, Marshall IG, Harvey AL: Depression of transmitter release and postjunctional sensitivity during neuromuscular block produced by antibiotics. Br J Anaesth 51:1027–1033, 1979

    Article  CAS  PubMed  Google Scholar 

  16. Fiekers JF: Effects of the aminoglycoside antibiotics, streptomycin and neomycin on neuromuscular transmission. 1. Presynaptic considerations. J Pharmacol Exp Ther 225:487–495, 1983a

    CAS  PubMed  Google Scholar 

  17. Fiekers JF: Effects of the aminoglycoside antibiotics, streptomycin and neomycin on neuromuscular transmission. II. Postsynaptic considerations. J Pharmacol Exp Ther 225:496–502, 1983b

    CAS  PubMed  Google Scholar 

  18. Foldes FF, Somogyi GT, Chaudhry IA, Nagashima H. Duncalf D: Assay of 3H acetylcholine release from mouse diaphragm without cholinesterase inhibition. Anesthesiology 61:A395, 1984

    Article  Google Scholar 

  19. Somogyi GT, Vizi ES, Chaudhry lA, Nagashima H, Duncalf D, Foldes FF, Goldiner PL: Modulation of stimulationevoked release of newly formed acetylcholine from mouse hemidiaphragm preparation. Naunyn-Schmiedeberg’s Arch Pharmacol 336:11–15, 1987

    Article  CAS  Google Scholar 

  20. Wessler I, Steilein O: Differential release of 3H-acetylcholine from the rat phrenic nerve-hemidiaphragm preparation by electrical nerve stimulation and by high potassium. Neuroscience 22:289–299, 1987

    Article  CAS  PubMed  Google Scholar 

  21. Vizi ES, Somogyi GT, Nagashima H, Duncalf D, Chaudhry lA, Földes FF: D-Tubocurarine and pancuronium inhibit evoked release of acetylcholine. Anesthesiology 63:A328, 1985

    Article  Google Scholar 

  22. Vizi ES, Somogyi GT: Prejunctional modulation of acetylcholine release from the skeletal neuromuscular junction: link between positive (nicotinic)-and negative (muscarinic) feedback modulation. Br J Pharmacol 97:65–70, 1989

    CAS  PubMed  Google Scholar 

  23. Moore EW: Ionized calcium in normal serum, ultrafiltrates, and whole blood determined by ion-exchange electrodes. J Clin Invest 49:319–324, 1970

    Article  Google Scholar 

  24. Foldes FF: The significance of physiological (Ca2+) and (Mg2+) for in vitro experiments on synaptic transmission. Life Sciences 28:1585–1590, 1981

    Article  CAS  PubMed  Google Scholar 

  25. Kilbinger H, Wessler I: Inhibition by acetylcholine of the stimulation-evoked release of3H-acetylcholine from the guineapig myenteric plexus. Neuroscience 5:1331–1340, 1980

    Article  CAS  PubMed  Google Scholar 

  26. Vizi ES, Ono K, Adam-Vizi V, Duncalf D, Földes FF: Presynaptic inhibitory effect of Met5-enkephalin onl4C-acetylcholine release from the myenteric plexus and its interaction with muscarinic negative feedback inhibition. J Pharmacol Exp Ther 230:493–499, 1984

    CAS  PubMed  Google Scholar 

  27. Vizi Es, Somogyi GT, Nagashima H, Duncalf D, Chaudhry IA, Kobayashi O, Goldiner PL, Földes, FF: Tubocurarine and Pancuronium inhibit evoked release of acetylcholine from the mouse hemidiaphragm preparation. Br J Anaesth 59:226–231, 1987

    Article  CAS  PubMed  Google Scholar 

  28. Zierlier KL: Mechanism of muscle contraction and its energetics. In: Mountcastle V.B. ed. Medical Physiology. St. Louis. C.V. Mosby, pp. 84–96, 1974

    Google Scholar 

  29. Foldes FF: The significance of physiological Ca2+ and Mg2+ for in vitro experiments on synaptic transmission. Life Sci 28:1585–1590, 1969

    Article  Google Scholar 

  30. Sokoll MD, Gergis SD: Antibiotics and neuromuscular function. Anesthesiology 55:148–159, 1979

    Article  Google Scholar 

  31. Vital-Brazil O, Prado-Franceschi J: The nature of neuromuscular block produced by neomycin and gentamicin. Arch Int Pharmacodyn Ther 179:78–85, 1969

    CAS  PubMed  Google Scholar 

  32. Vizi ES, Vyskocil F: Changes in total and quantal release of acetylcholine in the mouse diaphragm during activation and inhibition of membrane ATPase. J Physiol (Lond) 286:1–14, 1979

    CAS  Google Scholar 

  33. Vizi ES, van Dijk K, Foldes FF: The effect of 4-aminopyridine on acetylcholine release. J Neural Trans 41:265–274, 1977

    Article  CAS  Google Scholar 

  34. Földes FF, Ludvig N, Nagashima H, Vizi ES: The influence of aminopiridines on Ca2+-dependent evoked release of acetylcholine from rat cortex slices. Neurochem Res 13:761–764, 1988

    Article  PubMed  Google Scholar 

  35. Paton WDM, Waud DR: The margin of safety of neuromuscular transmission. J Physiol 191:59–90, 1967

    CAS  PubMed  Google Scholar 

  36. Waud BE, Waud DR: The relation between the response to “train of four” stimulation and receptor occlusion during competitive neuromuscular block. Anesthesiology 37:413–416, 1972

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

About this article

Cite this article

Vizi, E.S., Chaudhry, I.A., Goldiner, P.l. et al. The pre- and postjunctional components of the neuromuscular effect of antibiotics. J Anesth 5, 1–9 (1991). https://doi.org/10.1007/s0054010050001

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s0054010050001

Key words

Navigation