Antibiotic-induced paralysis of the mouse phrenic nerve-hemidiaphragm preparation, and reversibility by calcium and by neostigmine

Abstract

Certain antibiotics can induce neuromuscular paralysis, but the mechanism of this action is largely unknown. The purpose of this study was to compare the neuromuscular blocking potencies and reversibilities of 16 antibiotics in the isolated mouse phrenic nerve-hemidiaphragm preparation. The antibiotics tested were five aminoglycosides (neomycin, gentamicin, streptomycin, dihydrostreptomycin and kanamycin), tetracycline and oxytetracycline, polymyxins B and E, penicillins G and V, cephradine, cephaloridine, erythromycin, lincomycin, and clindamycin. Reversibility of the muscle paralysis by calcium and neostigmine was assessed. All the aminoglycosides resembled magnesium in blocking neuromuscular transmission, the neuromuscular blockade being almost completely reversed (to 64-77 per cent of control) by calcium but only poorly reversed by neostigmine (to 20-67 per cent of control). Neuromuscular blockade produced by the tetracyclines was also reversed by calcium (44-104 per cent) but not by neostigmine (0-15 per cent). Neuromuscular blockade produced by the polymyxins or by lincomycin was only partially reversed by calcium (0-34 per cent). Penicillin V, erythromycin, clindamycin, polymyxin B and the tetracyclines could also produce muscle paralysis by decreasing muscle contractility. This effect on contractility was irreversible by pharmacologic means. Penicillin G, cephradine and cephaloridine possessed negligible paralyzing effects on the nerve-muscle preparation. It is concluded that the different groups of antibiotics tested act by different mechanisms and that only the calcium-induced reversal of aminoglycoside block is predictable.