Cardiovascular and neurological effects of laudanosine. Studies in mice and rats, and in conscious and anaesthetized dogs

The effects of laudanosine, a metabolite of atracurium, on the behaviour of conscious mice, rats and dogs, and on cardiovascular function in conscious and anaesthetized dogs have been evaluated: EEG studies were performed in anaesthetized dogs. In mice and rats, i.v. bolus doses of laudanosine 10-20 mg kg-1, caused convulsions and hind limb extensions; these effects were prevented by pretreatment with diazepam. After the continuous infusion of laudanosine to conscious dogs, plasma concentrations in the order of 1.2 micrograms ml-1 did not cause behavioural disturbances. In anaesthetized dogs, laudanosine plasma concentrations of more than 6 micrograms ml-1 caused hypotension and bradycardia, laudanosine concentrations greater than 10 micrograms ml-1 induced epileptic EEG spiking and plasma concentrations greater than 17 micrograms ml-1 produced prolonged seizures. There is a wide difference between laudanosine plasma concentrations in patients given atracurium by bolus injection or by short-term infusion for surgical use and those required to induce epileptic activity in dogs. However, during the prolonged infusion of atracurium to patients this difference will be decreased. It is unlikely that the use of atracurium, in patients, would result in plasma concentrations of laudanosine capable of producing neurological or cardiovascular disturbances.