Neurotoxicity of a novel local anesthetic agent, ropivacaine: the possible roles of bursts of potential and cytoplasmic second messenger.
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.
Lin
Pei-Lin
PL
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Fan
Shou-Zen
SZ
Tsai
Feng-Fong
FF
Tsai
Ming-Cheng
MC
Lin
Chia-Hsien
CH
Huang
Chi-Hsiang
CH
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
D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine