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 cardiovascul ar 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 pro duced the predetermined toxic endpoints (i.e. seizure activity on EEG, isoelectric EEG, cardiac arrhythmia on ECG, asystole on ECG) at signi ficantly lower doses than 2-chloroprocaine (P < 0.05). The mean dose o f 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 rat e of decrease of mean arterial blood pressure during the infusion was significantly faster with prilocaine (P < 0.01). Typically, arrhythmia s did not appear until just before asystole, suggesting that neither o f the local anaesthetics possessed marker arrhythmogenic properties. I t is concluded that prilocaine is slightly more toxic than 2-chloropro caine 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).