Syvälahti E K, Kunelius R, Laurén L
Department of Pharmacology, University of Turku, Finland.
Pharmacol Toxicol. 1988 Feb;62(2):90-4. doi: 10.1111/j.1600-0773.1988.tb01852.x.
The anticholinergic antiparkinsonian drugs biperiden, benztropine, trihexyphenidyl, methixene, and procyclidine were compared with atropine and pirenzepine, as well as with orphenadrine, amantadine and some standard antidepressives and neuroleptics in their ability to inhibit the binding of tritiated quinuclidinyl benzilate (QNB) to the muscarinic receptors in rat brain cortical tissue. Most of the antiparkinsonian drugs studied were potent inhibitors of (-)3H-QNB binding, when compared to atropine (IC50-value = 0.22 microM), the IC50-values ranging from 0.0084 microM (biperiden) to 0.07 microM (procyclidine). Orphenadrine had a low and amantadine no evident affinity for muscarinic receptors. With the exception of pirenzepine and biperiden the inhibition curves were steep and parallel, giving linear Hill plots with coefficients close to unity. The binding profile of atropine, pirenzepine, and biperiden was further studied in heart and lung tissues, atropine showing only small divergences in its binding to the different tissues, but biperiden and pirenzepine having five to ten times lower affinity in the peripheral tissues than in the brain. The results confirm the high affinity of most of the antiparkinsonian drugs for brain muscarinic receptors. The dissociation constants agree with the average clinical doses of the drugs. It must be remembered, however, that the binding data may represent multiple events at receptor sites because most of the drugs used are mixtures of stereoisomers. Thus further studies using individual enantiomers are needed to compare more directly binding data between the compounds.
将抗胆碱能抗帕金森病药物比哌立登、苯海索、苯甲托品、甲哌噻吨和丙环定与阿托品、哌仑西平以及奥芬那君、金刚烷胺和一些标准抗抑郁药及抗精神病药进行了比较，观察它们抑制氚标记的奎宁环基苯甲酸酯（QNB）与大鼠脑皮质组织中毒蕈碱受体结合的能力。与阿托品（IC50值 = 0.22微摩尔）相比，大多数所研究的抗帕金森病药物都是（-）3H-QNB结合的强效抑制剂，IC50值范围从0.0084微摩尔（比哌立登）到0.07微摩尔（丙环定）。奥芬那君对毒蕈碱受体的亲和力较低，金刚烷胺则无明显亲和力。除哌仑西平和比哌立登外，抑制曲线陡峭且平行，希尔图呈线性，系数接近1。进一步研究了阿托品、哌仑西平和比哌立登在心脏和肺组织中的结合情况，阿托品在不同组织中的结合仅显示出微小差异，但比哌立登和哌仑西平在外周组织中的亲和力比在脑中低五到十倍。结果证实了大多数抗帕金森病药物对脑毒蕈碱受体具有高亲和力。解离常数与药物的平均临床剂量相符。然而，必须记住，结合数据可能代表受体部位的多种事件，因为所使用的大多数药物都是立体异构体的混合物。因此，需要使用单个对映体进行进一步研究，以便更直接地比较化合物之间的结合数据。
