Cumulation of neomycin and its residual potentiation of tubocurarine in the cat.
Cumulation and interaction of neuromuscular blocking effects of neomycin and tubocurarine were determined on responses of the tibialis anterior muscle of the anaesthetized cat to indirect stimulation. Neuromuscular block produced by neomycin was cumulative despite rapid and apparent full recovery of twitch tension and an interval of 3 h between dose-response studies. Ed50 of neomycin on twitch tension decreased (P less than 0.05) from 22 +/- 4 mg kg-1 to 12 +/- 3 mg kg-1 after 3 h; marked post-tetanic exhaustion was observed after the antibiotic. Neuromuscular block (80-90%) with neomycin 25-30 mg kg-1 followed by full recovery and 3-h interval decreased (P less than 0.05) the ED50 of tubocurarine on twitch tension from 0.2 +/- 0.02 mg kg-1 to 0.13 +/- 0.03 mg kg-1. Tubocurarine exhibited no cumulative effects at intervals of 2 h and did not significantly affect the response of twitch and tetanic tension to neomycin after an interval of 2 h. It is concluded that neomycin increases the sensitivity of neuromuscular transmission to tubocurarine despite apparently normal responses to indirect stimulation and that the post-tetanic exhaustion observed with neomycin alone may explain apnoea reported in patients with the antibiotic.
D000818:Animals; D002415:Cats; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D008297:Male; D009355:Neomycin / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000187:drug effects; D013997:Time Factors; D014403:Tubocurarine / Q000494:pharmacology*
D009355:Neomycin; D014403:Tubocurarine