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东莨菪碱是当前抗晕动病最强的单药,但有明显的不良反应。根据“抗胆碱药的中枢解胆碱能活性大小并不与其不良反应相平行”的假设,作者设计、合成了一系列氮杂双环醇的羧酸酯类化合物。其中由α-苯基-α-环戊基-α-羟基乙酸甲酯与N-甲基-3-氮杂双环(3 ,3 ,1)壬-9α-醇的酯交换反应制得的盐酸苯环壬酯在动物模型上,等效抗晕剂量时,其不良反应较中枢解胆碱能抗晕动病药东莨菪碱和地芬尼多为轻。临床试验表明,志愿者口服该药(每人2 ~4 mg)后,其预防晕车晕船的总有效率显著高于安慰剂对照组和阳性对照药地芬尼多组(口服每人25 ~50 mg)。在转椅致晕动症的志愿者自身对照试验中,苯环壬酯和地芬尼多都能显著减少旋转引起的眼电震图和胃电图异常改变。在另一组自身对照的旋转致晕动症人体试验中,苯环壬酯和东莨菪碱都能明显减少旋转引起的胃电活动异常,减少急性晕动病的Graybiel得分和抑制视-前庭-内耳反应。苯环壬酯每人2和4 mg的效用相当于东莨菪碱每人0 .3和0 .6 mg的效用。在易感空晕病的飞行学员中,苯环壬酯(每人3 mg)明显缩短习服空晕病所需的时间,并且在停药后其习服水平没有明显下降。苯环壬酯的不良反应主要是轻度口干(发生率9 .7 %)和轻度思睡(9 .97 %,仅发生于晕车晕船试验中)。苯环壬酯是一个中枢解胆碱能抗晕动病新药,较地芬尼多和东莨菪碱抗晕效果更好,中枢不良反应更低。
Scopolamine is currently the strongest single anti-motion sickness, but there are obvious adverse reactions. Based on the hypothesis that the central cholinergic activity of anticholinergic drugs is not parallel to its adverse reaction, the authors designed and synthesized a series of azocobicyclic carboxylic acid ester compounds. Hydrochloric acid obtained by the transesterification reaction of methyl α-phenyl-α-cyclopentyl-α-hydroxyacetate with N-methyl-3-azabicyclo (3,3,1) nonane-9α-alcohol Phencynonate in animal models, the equivalent anti-halo doses, the adverse reactions than the central cholinergic anti-motion sickness scopolamine and defenidyl light. Clinical trials showed that the total effective rate of volunteers in preventing motion sickness and seasickness after oral administration of the drug (2 ~ 4 mg per person) was significantly higher than that of the placebo control group and the positive control drug phenylephrine group (oral administration of 25 to 50 mg). In the self-controlled trials of volunteers who had dyskinesia in the swivel chair, neither phencynonate nor dendivudine significantly reduced ocular and electrogastrogram changes due to rotation. In another set of self-controlled, rotationally-induced motion sickness tests, both phencynonate and scopolamine significantly reduced rotational abnormalities in gastric electrical activity, decreased Graybiel scores for acute motion sickness, and suppressed visual-vestibular-inner ear responses . The efficacy of phencynonate at 2 and 4 mg per person corresponds to 0.3 and 0.6 mg of scopolamine per person. Phencynonate (3 mg per person) significantly reduced the time required for accretion of an airspace sickness among pilots who were susceptible to an airsickness, and their levels of acclimation did not decrease significantly after discontinuation. The adverse reactions of phencynonate were mild dry mouth (incidence 9.7%) and mild sleepiness (9.97%, only occurred in motion sickness seasickness test). Phencynonate is a central anticholinergic anti-motion sickness new drugs, more than phenanthridine and scopolamine anti-corona effect is better, central adverse reactions lower.