Kawabata K, Sumikawa K, Kamibayashi T, Fukumitsu K, Hayashi Y, Takada K, Yoshiya I
Department of Anesthesiology, Osaka University Medial School, Japan.
J Pharm Pharmacol. 1993 Jul;45(7):632-5. doi: 10.1111/j.2042-7158.1993.tb05667.x.
This study was carried out to determine the relative potencies of local anesthetics to inhibit the cholinergic synaptic transmission using cultured bovine adrenal chromaffin cells, and to clarify if the inhibitory action would correlate with biophysical and pharmacological properties. Local anaesthetics (bupivacaine, etidocaine, tetracaine, lignocaine and procaine; 0.02-2 mM) inhibited carbachol-induced catecholamine release from the cells in a concentration-dependent manner. This inhibition was completely reversible. IC50 (concentration of 50% inhibition) of each anaesthetic showed no correlation with the lipid solubility. The local anaesthetics showed greater inhibitory potency at a higher extracellular pH. The results suggest that clinically relevant concentrations of local anaesthetics inhibit the stimulus-secretion coupling in the chromaffin cells. The un-ionized based form plays a major role, and the inhibitory potency does not depend on the lipid solubility of the anaesthetics.
本研究旨在利用培养的牛肾上腺嗜铬细胞确定局部麻醉药抑制胆碱能突触传递的相对效能，并阐明这种抑制作用是否与生物物理和药理学特性相关。局部麻醉药（布比卡因、依替卡因、丁卡因、利多卡因和普鲁卡因；0.02 - 2 mM）以浓度依赖性方式抑制卡巴胆碱诱导的细胞儿茶酚胺释放。这种抑制作用是完全可逆的。每种麻醉药的IC50（50%抑制浓度）与脂溶性无关。局部麻醉药在较高的细胞外pH值时显示出更大的抑制效能。结果表明，临床相关浓度的局部麻醉药抑制嗜铬细胞中的刺激-分泌偶联。非离子化形式起主要作用，抑制效能不取决于麻醉药的脂溶性。
