Pérez-Guillermo F, Delgado E M, Vidal C J
Departamento de Bioquímica, Facultad de Biología, Universidad de Murcia, Spain.
Biochem Pharmacol. 1987 Nov 1;36(21):3593-6. doi: 10.1016/0006-2952(87)90007-4.
The effects of tertiary amine local anesthetics (procaine, mepivacaine, lidocaine, tetracaine, dibucaine, and bupivacaine) and chlorpromazine were investigated for rabbit muscle acetylcholinesterase and human serum cholinesterase. The muscle enzyme was poorly inhibited by local anesthetics containing an amide linkage. The serum cholinesterase was inhibited by all those compounds, their relative potencies being proportional to their octanol/water partition coefficients. The dissociation constants of tetracaine and procaine, ester anesthetics, were 1000-fold and 100-fold, respectively, that which would be expected from their partition coefficient basis respective to the other amide anesthetics. Procaine showed competitive inhibition of serum cholinesterase, whereas for most anesthetics a mixed type of inhibition was observed. Procaine probably binds at the main anionic site, while the other positively charged anesthetics bind to either the catalytic centre or to the peripheral or modulator anionic site, modifying the kinetic behaviour of cholinesterase as has been demonstrated by the appearance of negative cooperativity for binding to the substrate.
研究了叔胺类局部麻醉药（普鲁卡因、甲哌卡因、利多卡因、丁卡因、地布卡因和布比卡因）及氯丙嗪对兔肌肉乙酰胆碱酯酶和人血清胆碱酯酶的影响。含酰胺键的局部麻醉药对肌肉酶的抑制作用较弱。血清胆碱酯酶受到所有这些化合物的抑制，它们的相对效力与其辛醇/水分配系数成正比。酯类麻醉药丁卡因和普鲁卡因的解离常数分别比其他酰胺类麻醉药基于分配系数预期的值高1000倍和100倍。普鲁卡因对血清胆碱酯酶表现出竞争性抑制，而大多数麻醉药观察到的是混合型抑制。普鲁卡因可能结合在主要阴离子位点，而其他带正电荷的麻醉药则结合到催化中心或外周或调节性阴离子位点，改变了胆碱酯酶的动力学行为，这已通过与底物结合时出现负协同性得到证明。
