Muir A W, Anderson K, Marshall R J, Booij L H, Crul J F, Prior C, Bowman W C, Marshall I G
Department of Pharmacology, Organon Laboratories Ltd., Newhouse, Lanarkshire, UK.
Acta Anaesthesiol Scand. 1991 Jan;35(1):85-90. doi: 10.1111/j.1399-6576.1991.tb03247.x.
Org 9991, a 16-N-homopiperidinium substituted vecuronium analogue, has been tested for neuromuscular blocking activity in anaesthetized cats, pigs, dogs and monkeys, and in isolated nerve-muscle preparations. Org 9991 exhibited non-depolarizing neuromuscular blocking activity of the competitive type, being reversible by neostigmine and showing no endplate channel blocking action in isolated preparations. In cats, 50% vagal block was observed at doses of Org 9991 approximately 10 times those producing 50% neuromuscular block; no ganglion block was seen at these doses. Effects on blood pressure or heart rate at 90% twitch blocking doses were either minor or absent. The potency and time course of action of Org 9991 remained similar in all four species: i.e. 90% block at ca 200-300 micrograms kg-1; onset time ca 1.2-1.9 min; duration 90% ca 4.5-8.9 min. This study suggests that 16-N-homopiperidinium analogues of vecuronium may provide leads in the quest for a potent non-depolarizing replacement for suxamethonium.
Org 9991是一种16-N-高哌啶鎓取代的维库溴铵类似物，已在麻醉的猫、猪、狗和猴子以及离体神经肌肉标本中测试其神经肌肉阻滞活性。Org 9991表现出竞争性非去极化神经肌肉阻滞活性，可被新斯的明逆转，且在离体标本中未显示终板通道阻滞作用。在猫中，产生50%神经肌肉阻滞的Org 9991剂量约为产生50%迷走神经阻滞剂量的10倍；在这些剂量下未观察到神经节阻滞。在90%颤搐阻滞剂量下对血压或心率的影响轻微或无影响。Org 9991在所有四个物种中的效力和作用时间进程相似，即约200 - 300微克/千克时90%阻滞；起效时间约1.2 - 1.9分钟；90%阻滞持续时间约4.5 - 8.9分钟。这项研究表明，维库溴铵的16-N-高哌啶鎓类似物可能为寻找一种有效的非去极化琥珀胆碱替代物提供线索。
