Effects of anticonvulsants on local anaesthetic-induced neurotoxicity in rats.
The effects of various anticonvulsants on local anaesthetics procaine- and lidocaine-induced convulsions were investigated in rats. Pretreatment with diazepam (2.5-5 mg/kg, intraperitoneally) and clonazepam (5-10 mg/kg, intraperitoneally) completely protected the rats against both local anaesthetic-induced convulsions. Phenobarbital (12.5-50 mg/kg, subcutaneously) also significantly decreased the incidence of both convulsions and prolonged their latencies. Carbabazepine (10-40 mg/kg, intraperitoneally) did not completely repress both convulsions, but it prolonged their latencies. Phenytoin (5-20 mg/kg, intraperitoneally) and primidone (30-60 mg/kg, intraperitoneally) markedly enhanced both local anaesthetic-induced convulsions, as shown by shortening of latency and increase in mortality. Valproate (100-200 mg/kg, intraperitoneally) produced a protective effect against procaine-induced convulsions, while it strongly enhanced lidocaine-induced convulsions. These results suggest that the benzodiazepines are effective drugs to prevent neurotoxicity induced by local anaesthetics, while phenytoin and primidone potentiate them.
Sawaki
K
K
Department of Pharmacology, Tokyo Dental College, Chiba, Japan. sawaki@tdc.ac.jp
Ohno
K
K
Miyamoto
K
K
Hirai
S
S
Yazaki
K
K
Kawaguchi
M
M
D000779:Anesthetics, Local / Q000633:toxicity*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D004357:Drug Synergism; D008012:Lidocaine / Q000633:toxicity; D008297:Male; D011343:Procaine / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D014635:Valproic Acid / Q000494:pharmacology
D000779:Anesthetics, Local; D000927:Anticonvulsants; D001569:Benzodiazepines; D011343:Procaine; D014635:Valproic Acid; D008012:Lidocaine