Jones S V, Marshall I G
Br J Anaesth. 1987 Jun;59(6):776-83. doi: 10.1093/bja/59.6.776.
The effects of disopyramide were studied at the neuromuscular junction in an attempt to elucidate the mechanism of its blocking action at this site. Disopyramide 5 X 10(-5) - 10(-3) mol litre-1 produced a concentration-dependent reduction of twitch amplitude in the indirectly stimulated chick biventer cervicis preparation, but greater concentrations were required to reduce twitches elicited directly in the presence of erabutoxin-b 1 microgram ml-1. Equieffective twitch blocking doses of either disopyramide or tubocurarine greatly reduced agonist responses to acetylcholine and carbachol, but the reduction was less for magnesium-blocked twitches. Neostigmine antagonized tubocurarine-induced, but not disopyramide-induced, blockade of twitches. Concentration-response profiles to acetylcholine and carbachol were shifted to the right in a non-parallel fashion and the maximal response was depressed by disopyramide 5 X 10(-5) - 10(-4) mol litre-1. Intracellular recording studies carried out in the cut, voltage-clamped costo-cutaneous muscle of the garter snake showed that disopyramide 5 X 10(-5) - 5 X 10(-4) mol litre-1 produced a concentration- and voltage-dependent reduction of the amplitude of neurally evoked endplate-currents (EPC) and of the time constant of decay (tau) of EPC. We conclude that disopyramide possesses a non-competitive blocking action at the neuromuscular junction, which is not reversible by anticholinesterase agents. The voltage-dependent nature of the block suggests that it is mediated via blockade of the open form of the acetylcholine-activated receptor-ion channel complex.
研究了丙吡胺在神经肌肉接头处的作用，以阐明其在此部位的阻断作用机制。丙吡胺5×10⁻⁵ - 10⁻³ mol/L可使间接刺激的鸡颈二腹肌标本的抽搐幅度呈浓度依赖性降低，但在存在1μg/ml erabutoxin-b的情况下，需要更高的浓度才能降低直接诱发的抽搐。丙吡胺或筒箭毒碱的等效抽搐阻断剂量可大大降低对乙酰胆碱和卡巴胆碱的激动剂反应，但对镁阻断的抽搐的降低作用较小。新斯的明可拮抗筒箭毒碱诱导的抽搐阻断，但不能拮抗丙吡胺诱导的抽搐阻断。对乙酰胆碱和卡巴胆碱的浓度-反应曲线以非平行方式向右移动，丙吡胺5×10⁻⁵ - 10⁻⁴ mol/L可降低最大反应。在切开并电压钳制的束带蛇肋皮肌中进行的细胞内记录研究表明，丙吡胺5×10⁻⁵ - 5×10⁻⁴ mol/L可使神经诱发的终板电流（EPC）幅度和EPC衰减时间常数（tau）呈浓度和电压依赖性降低。我们得出结论，丙吡胺在神经肌肉接头处具有非竞争性阻断作用，抗胆碱酯酶药物不能使其逆转。阻断的电压依赖性表明它是通过阻断乙酰胆碱激活的受体-离子通道复合物的开放形式介导的。
