Effects of cimetidine and ranitidine on local anesthetic central nervous system toxicity in mice.
The effects of cimetidine (5-200 mg/kg), ranitidine (1-100 mg/kg), or saline on local anesthetic central nervous system toxicity was studied when administered 20 min before the administration of lidocaine (30-80 mg/kg) or 2-chloroprocaine (50-250 mg/kg) to female white CD-1 mice. All drugs were administered intraperitoneally. The 50% convulsive dose (CD50) was determined for each drug and dose combination. Pretreatment with cimetidine resulted in a significant, dose-dependent decrease in the CD50 of lidocaine, whereas ranitidine pretreatment did not significantly alter the lidocaine CD50. A dose of cimetidine (15 mg/kg) that caused a significant decrease in 2-chloroprocaine CD50 (from 180 to 110 mg/kg) caused only an insignificant decrease in lidocaine CD50 (from 59 to 54 mg/kg). If these results can be applied to clinical doses in humans, ranitidine may be a safer premedicant than cimetidine with regard to interactions with local anesthetics.
D000779:Anesthetics, Local / Q000633:toxicity*; D000818:Animals; D001927:Brain Diseases / Q000139:chemically induced*; D002927:Cimetidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D008012:Lidocaine / Q000633:toxicity; D051379:Mice; D011343:Procaine / Q000031:analogs & derivatives / Q000633:toxicity; D011899:Ranitidine / Q000494:pharmacology*; D012640:Seizures / Q000139:chemically induced
D000779:Anesthetics, Local; D011343:Procaine; C004616:chloroprocaine; D002927:Cimetidine; D011899:Ranitidine; D008012:Lidocaine