Depression of transmitter release and postjunctional sensitivity during neuromuscular block produced by antibiotics

In an attempt to elucidate the mechanisms by which antibiotics induce muscle paralysis, the effects of streptomycin, lincomycin, polymyxin B and clindamycin were investigated in the mouse phrenic nerve-hemidiaphragm preparation. Streptomycin resembled magnesium in reducing miniature endplate potential (m.e.p.p.) amplitude and frequency, whereas lincomycin, clindamycin and polymyxin B resembled tubocurarine in abolishing m.e.p.p. Endplate potential (e.p.p.) quantal content in streptomycin was 9, similar to that found in magnesium (5), whereas quantal contents in lincomycin (42), polymyxin B (37) and clindamycin (32) lay between values found in magnesium and in tubocurarine (123). Control quantal content was 152. In the presence of a mixture of magnesium and tubocurarine, no m.e.p.p. could be recorded and quantal content was 39. Blockade of twitches by a mixture of magnesium and tubocurarine was more successfully reversed by a mixture of calcium and neostigmine (to 70% of control) than by either calcium (to 49% of control) or by neostigmine (to 30% of control) alone. Lincomycin- and polymyxin B-induced blockades were poorly reversed by a mixture of the two reversal agents. It is concluded that streptomycin has a magnesium-like action whereas lincomycin, clindamycin and polymyxin B have relatively greater postjunctional and less prejunctional blocking activities. However, the effects of lincomycin and polymyxin B were not analogous to those of a tubocurarine-magnesium mixture, and their mechanism of action is still unclear. Clindamycin produced effects compatible with local anaesthetic activity.