title: Neurotoxicity of a novel local anesthetic agent, ropivacaine: the possible roles of bursts of potential and cytoplasmic second messenger.
abstract: OBJECTIVE
  Ropivacaine has been shown to induce convulsion following overdose or accidental intravenous injection, but the mechanisms are poorly understood. Using an identifiable central neuron from giant African snail, the authors studied the mechanism of ropivacaine-elicited bursts of potential and explored the possible mechanisms of ropivacaine-induced neurotoxicity.
  
  
  METHODS
  Ropivacaine action on a central neuron (RP4) of the giant African snail (Achatina fulica Ferussac) was recorded by conventional electrophysiologic technique. Interactions between ropivacaine and prazosin, propranolol, atropine, d-tubocurarine, calcium-free solution, H89, U73,122, neomycin, high-magnesium solution, and chelerythrine were also observed.
  
  
  RESULTS
  The RP4 neuron showed spontaneous firing of action potentials. Extracellular application of ropivacaine (900 microM) reversibly elicited bursts of potential in the RP4 neuron. The bursts of potential elicited by ropivacaine were not blocked after administration of: (1) prazosin, propranolol, atropine, d-tubocurarine; (2) calcium-free solution; and (3) pretreatment with H89 or chelerythrine. The bursts of potential elicited by ropivacaine were blocked by pretreatment with U73122 (30 microM) or by adding neomycin (3.5 mM) or high-magnesium solution (30 mM).
  
  
  CONCLUSIONS
  Ropivacaine reversibly elicited bursts of potential in the central snail neuron. The ropivacaine-elicited bursts of potential were associated with phospholipase C activity in the RP4 snail neuron. Our results suggest that ropivacaine-induced neurotoxicity is highly associated with phospholipase C activity and phospholipase C inhibitor may offer a novel therapeutic approach for managing local anesthetic-induced convulsion or other transient neurologic toxicity.
authors.affiliation: Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Pei-Lin
authors.initials: PL
authors.lastname: Lin
authors.forename: Shou-Zen
authors.initials: SZ
authors.lastname: Fan
authors.forename: Feng-Fong
authors.initials: FF
authors.lastname: Tsai
authors.forename: Ming-Cheng
authors.initials: MC
authors.lastname: Tsai
authors.forename: Chia-Hsien
authors.initials: CH
authors.lastname: Lin
authors.forename: Chi-Hsiang
authors.initials: CH
authors.lastname: Huang
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000577:Amides / Q000009:adverse effects*; D000779:Anesthetics, Local / Q000009:adverse effects*; D000818:Animals; D023421:Models, Animal; D009474:Neurons / Q000187:drug effects*; D000077212:Ropivacaine; D015290:Second Messenger Systems / Q000187:drug effects*; D012908:Snails
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine