Comparison of acute central nervous system and cardiovascular toxicity of 2-chloroprocaine and prilocaine in the rat.
In this study, we compared the central nervous system and cardiovascular system toxicity of i.v. administered 0.5% 2-chloroprocaine (N = 10) and 0.5% prilocaine (N = 10) in lightly anaesthetised rats. Arterial blood pressure, ECG and EEG were continuously recorded. Prilocaine produced the predetermined toxic end-points (i.e. seizure activity on EEG, isoelectric EEG, cardiac arrhythmia on ECG, asystole on ECG) at significantly lower doses than 2-chloroprocaine (P < 0.05). The mean dose of prilocaine producing asystole was 166 mg.kg-1 (+/- 45 mg.kg-1, s.d.) vs. 255 mg.kg-1 (+/- 42 mg.kg-1) for 2-chloroprocaine (P < 0.01). The rate of decrease of mean arterial blood pressure during the infusion was significantly faster with prilocaine (P < 0.01). Typically, arrhythmias did not appear until just before asystole, suggesting that neither of the local anaesthetics possessed marker arrhythmogenic properties. It is concluded that prilocaine is slightly more toxic than 2-chloroprocaine in the rat, but that both local anaesthetics have a wide margin of safety. Doses producing seizure activity on the EEG (prilocaine 53 mg.kg-1 and 2-chloroprocaine 70 mg.kg-1, on average) are much higher than those used in clinical practice (usually < 10 mg.kg-1).
Rosenberg
P H
PH
Department of Anaesthesiology, Helsinki University Central Hospital, Finland.
Zou
J
J
Heavner
J E
JE
D000779:Anesthetics, Local / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects*; D002490:Central Nervous System / Q000187:drug effects*; D007262:Infusions, Intravenous; D011318:Prilocaine / Q000008:administration & dosage / Q000633:toxicity*; D011343:Procaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley
D000779:Anesthetics, Local; D011318:Prilocaine; D011343:Procaine; C004616:chloroprocaine