title: Calcium and neostigmine antagonize gentamicin, but augment clindamycin-induced tetanic fade in rat phrenic nerve-hemidiaphragm preparations.
abstract: OBJECTIVE
  A reduction in acetylcholine release induced by gentamicin may limit neostigmine-induced increases in acetylcholine concentration in the neuromuscular junction. An increase in acetylcholine concentration caused by neostigmine and calcium may enhance the use-dependent ion channel block of the nicotinic acetylcholine receptor caused by clindamycin. The purpose of this study was to determine whether calcium and neostigmine antagonize the neuromuscular blockade caused by gentamicin and augment the blockade caused by clindamycin during both single-twitch (0.1 Hz) and tetanic stimulation (50 Hz for 1.9 s).
  
  
  METHODS
  Left phrenic nerve-hemidiaphragm preparations (Male Sprague-Dawley rats, 150-250 g) were mounted in Krebs solution. The concentration-response curves of gentamicin and clindamycin were obtained. The reversal effects of treatment with 5 mM calcium or 250 nM neostigmine on the effects of 1.5 mM gentamicin, which caused 72% reduction of single twitch, were studied. The effects of calcium or neostigmine on the effects of clindamycin were studied by examining the shift of the concentration-response curve of clindamycin with pretreatments with these agents. The effective concentrations were determined by a probit model.
  
  
  RESULTS
  Calcium antagonized the single-twitch depression and tetanic fade caused by gentamicin more effectively than neostigmine. The effective concentration of 50% maximal effect (EC(50)) values of clindamycin for tetanic fade in the presence of 5 mM calcium or 250 nM neostigmine were reduced by approximately 52%.
  
  
  CONCLUSIONS
  Clindamycin and gentamicin interfere with neuromuscular transmission and cause tetanic fade. Neostigmine and calcium antagonized the neuromuscular blockade caused by gentamicin, but augmented that caused by clindamycin.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Dong-A University Medical Center and Medicine College, 1,3 Ka, Dongdaeshin-Dong, Seo-Gu, Busan, 602-715, Korea.
authors.forename: Soo-Il
authors.initials: SI
authors.lastname: Lee
authors.forename: Jong-Hwan
authors.initials: JH
authors.lastname: Lee
authors.forename: Seung Cheol
authors.initials: SC
authors.lastname: Lee
authors.forename: Jung Moo
authors.initials: JM
authors.lastname: Lee
authors.forename: Ji Hyeon
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology*; D002981:Clindamycin / Q000494:pharmacology*; D003964:Diaphragm / Q000187:drug effects; D004558:Electric Stimulation; D005839:Gentamicins / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects*; D009388:Neostigmine / Q000494:pharmacology*; D019148:Neuromuscular Blockade; D010243:Paralysis / Q000139:chemically induced / Q000517:prevention & control; D010277:Parasympathomimetics / Q000494:pharmacology*; D010791:Phrenic Nerve / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D010277:Parasympathomimetics; D009388:Neostigmine; D002981:Clindamycin; D002118:Calcium