Takeda M
Jpn J Pharmacol. 1976 Feb(1):13-9. doi: 10.1254/jjp.26.13.
The local anesthetic activities of cis- and trans- dl-1-benzoyloxy-2-dimethylamino-1,2,3,4-tetrahydronaphthalene were compared using several methods with guinea-pigs. The cis compound (YAU-17) was 2.9 to 6 times as potent as its trans isomer and exceeded procaine, lidocaine and cocaine in potencies of corneal anesthesia, intracutaneous anesthesia and sciatic nerve block. In another experiment on isolated frog sartorius muscle, all of the local anesthetics suppressed the twitch contractions elicited by stimulation of the sciatic nerve. The neuromuscular blocking activity of the cis compound was more pronounced than that of the trans form. Supersensitivity to noradrenaline was produced by both of the stereoisomers in isolated vas deferens of guinea-pigs although there was no difference in the activity. The sensitizing action was also demonstrable with cocaine and lidocaine but not with procaine. When injected intravenously into mice, the cis compound was twice as toxic as its isomer. It is postulated that stereoselectivity is to some extent involved in the mechanisms of action of the local anesthetic agents.
使用几种方法对豚鼠进行实验，比较了顺式和反式dl-1-苯甲酰氧基-2-二甲基氨基-1,2,3,4-四氢萘的局部麻醉活性。顺式化合物（YAU-17）的效力是其反式异构体的2.9至6倍，在角膜麻醉、皮内麻醉和坐骨神经阻滞效力方面超过了普鲁卡因、利多卡因和可卡因。在另一项对离体青蛙缝匠肌的实验中，所有局部麻醉药均抑制了刺激坐骨神经引起的抽搐收缩。顺式化合物的神经肌肉阻滞活性比反式化合物更明显。两种立体异构体在豚鼠离体输精管中均产生对去甲肾上腺素的超敏反应，尽管活性没有差异。可卡因和利多卡因也有这种致敏作用，但普鲁卡因没有。当静脉注射到小鼠体内时，顺式化合物的毒性是其异构体的两倍。据推测，立体选择性在某种程度上参与了局部麻醉药的作用机制。
