ISSN:
1438-8359
Keywords:
Neuromuscular junction
;
Margin of safety
;
Acetylcholine release
;
Presynaptic effect
;
Antibiotic
;
Neomycin
;
Diaphragm
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract The relative contributions of the pre- and postsynaptic components of the myoneural blocking effect of different antibiotics were studied using: (a) a radio-active method that measures selectively the Ca2+-dependent, stimulation evoked, quantally released, 3H-acetylcholine (3H-ACh) from the mouse in 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 of 3H-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 d-tubocurarine (d-Tc)-induced inhibition of the release of 3H-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 of 3H-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. (Vizi ES, Chaudhry IA, Goldiner PL, et al.: The pre- and postjunctional components of the neuromuscular effect of antibiotics. J Anesth 5: 1–9, 1991)
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s0054010050001
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