Kimura M, Kimura I, Muroi M, Nojima H, Diwan P V
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Biol Pharm Bull. 1995 May;18(5):691-5. doi: 10.1248/bpb.18.691.
The mode of the neuromuscular blocking action of coryneine (a quaternary ammonium derivative of dopamine) derived from aconite root was investigated in isolated phrenic nerve-diaphragm muscles and denervated diaphragm muscles of mice. Coryneine (20-150 microM) blocked the nerve-evoked twitch response without affecting the contraction evoked by electrical stimulation of the muscle. The blocking effect was reversed by neostigmine, a cholinesterase inhibitor. The electrical charge-response curve on depolarization produced by iontophoretically applied acetylcholine (ACh) at the endplate regions in normal muscles was shifted to the right on decreasing the maximal response by 40 microM coryneine. The double-reciprocal plot revealed that coryneine reduced the apparent affinity of ACh for its receptor on decreasing the maximal response. Coryneine (20 microM-2mM) itself depolarized the endplate membrane and this effect was reversibly suppressed by 1 and 5 microM pancuronium. Coryneine 30 microM-10mM) produced contractions of denervated muscles in a concentration-dependent manner and the effects were reduced by 70nM pancuronium. These results indicate that coryneine is a depolarizing agent and a mixed-type competitive and noncompetitive neuromuscular blocker.
研究了从乌头根中提取的可力丁（一种多巴胺季铵衍生物）在小鼠离体膈神经-膈肌和去神经支配的膈肌中的神经肌肉阻滞作用方式。可力丁（20 - 150微摩尔）阻断神经诱发的抽搐反应，而不影响肌肉电刺激诱发的收缩。该阻断作用可被胆碱酯酶抑制剂新斯的明逆转。在正常肌肉终板区域，通过离子导入法施加乙酰胆碱（ACh）产生的去极化的电荷-反应曲线，在40微摩尔可力丁使最大反应降低时向右移动。双倒数图显示，可力丁在降低最大反应时降低了ACh对其受体的表观亲和力。可力丁（20微摩尔 - 2毫摩尔）本身使终板膜去极化，这种作用可被1和5微摩尔泮库溴铵可逆性抑制。可力丁（30微摩尔 - 10毫摩尔）以浓度依赖的方式使去神经支配的肌肉收缩，且70纳摩尔泮库溴铵可减弱其作用。这些结果表明，可力丁是一种去极化剂，也是一种混合型竞争性和非竞争性神经肌肉阻滞剂。
