Cardiovascular and neurological effects of laudanosine. Studies in mice and rats, and in conscious and anaesthetized dogs.
Cardiovascular and neurological effects of laudanosine. Studies in mice and rats, and in conscious and anaesthetized dogs.
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劳丹诺辛对心血管和神经系统的影响。
DOI：
10.1093/bja/59.2.218
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发表时间：
1987
影响因子：
9.8
通讯作者：
P. L. Wheatley
中科院分区：
文献类型：
--
作者：
D. Chapple;A. Miller;J. Ward;P. L. Wheatley
已评价了劳丹诺新（阿曲库铵的代谢产物）对清醒小鼠、大鼠和犬的行为以及对清醒和麻醉犬的心血管功能的影响：在麻醉犬中进行EEG研究。在小鼠和大鼠中，静脉推注剂量为10-20 mg kg-1的劳丹诺新引起惊厥和后肢伸展;这些作用可通过地西泮预处理预防。清醒的狗连续输注劳丹诺新后，血浆浓度在1.2微克ml-1的顺序没有引起行为障碍。在麻醉的狗，劳丹诺新血浆浓度超过6微克ml-1引起低血压和心动过缓，劳丹诺新浓度大于10微克ml-1诱导癫痫EEG尖峰和血浆浓度大于17微克ml-1产生长期癫痫发作。通过推注或短期输注给予阿曲库铵用于外科手术的患者中的劳丹诺新血浆浓度与诱导犬癫痫活动所需的劳丹诺新血浆浓度之间存在很大差异。然而，在患者长期输注阿曲库铵期间，这种差异将减小。在患者中使用阿曲库铵不太可能导致能够产生神经或心血管紊乱的劳丹诺新血浆浓度。
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.