Ekström P, Kanje M, Edström A
Acta Physiol Scand. 1982 Oct;116(2):121-5. doi: 10.1111/j.1748-1716.1982.tb07119.x.
Various phenothiazines (thioridazine, trifluoperazine and chlorpromazine) and dibenzazepines (lofepramine, amitriptyline and desipramine) were studied for effects on fast axonal transport (AXT) in vitro in frog sciatic nerves. AXT, measured as the accumulation of (3H) leucine-labelled proteins in front of a ligature, was inhibited by more then 50% by all the drugs tested at 0.2 mM concentrations. Thioridazine and lofepramine were the most potent inhibitors. These effects were not due to decreased ganglionic incorporation. Some of the drugs also reduced the levels of high energy phosphates, adenosinetriphosphate (ATP) and creatinephosphate (CrP), but not to an extent which is likely to explain the arrested AXT. The polymerization of purified brain tubulin was inhibited by the phenothiazines but unaffected by the dibenzazepines at concentrations which inhibited AXT. Phenothiazines and dibenzazepines are chemically related and known to have a high affinity for calmodulin. The possibility that these drugs interefere with calmodulin regulated processes of importance for AXT will be discussed.
研究了多种吩噻嗪类药物（硫利达嗪、三氟拉嗪和氯丙嗪）及二苯氮䓬类药物（洛非帕明、阿米替林和地昔帕明）对青蛙坐骨神经体外快速轴突运输（AXT）的影响。以（3H）亮氨酸标记的蛋白质在结扎线前的积累来衡量AXT，所有受试药物在0.2 mM浓度时均可使AXT受到超过50%的抑制。硫利达嗪和洛非帕明是最有效的抑制剂。这些作用并非由于神经节摄取减少所致。部分药物还降低了高能磷酸盐、三磷酸腺苷（ATP）和磷酸肌酸（CrP）的水平，但降低程度不太可能解释AXT的停滞。在抑制AXT的浓度下，吩噻嗪类药物可抑制纯化的脑微管蛋白聚合，而二苯氮䓬类药物则无此作用。吩噻嗪类药物和二苯氮䓬类药物在化学上相关，且已知对钙调蛋白具有高亲和力。将讨论这些药物是否干扰对AXT至关重要的钙调蛋白调节过程。
