Eltze M, Figala V
Department of Pharmacology, Byk Gulden Pharmaceuticals, Konstanz, F.R.G.
Eur J Pharmacol. 1988 Dec 6;158(1-2):11-9. doi: 10.1016/0014-2999(88)90247-6.
The affinity of both the (+)- and the (-)-stereoisomer of biperiden for different muscarinic receptor subtypes was investigated in vitro in functional studies with field-stimulated rabbit vas deferens (M1-receptor), guinea-pig ileum (smooth muscle M2 beta-receptor) and rat left atrium (cardiac M2 alpha-receptor). (+)-Biperiden had its highest affinity to M1-receptors (pA2 = 9.07), had low affinity to cardiac M2 alpha-receptors (pA2 = 7.25) and intermediate affinity to ileal M2 beta-receptors (pA2 = 8.27). The ability of (+)-biperiden to discriminate between ileal M2 beta- and cardiac M2 alpha-receptors (factor = 10) was similar to that of 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, factor = 9). In contrast, (-)-biperiden displayed low but nearly undistinguishable affinity for all muscarinic receptor subtypes studied (pA2 = 5.59 +/- 6.38). (+)-Biperiden discriminated strongly between M1- and cardiac M2 alpha-receptors (factor 66), thus being even more selective than pirenzepine (factor 28) which makes it one of the most M1-/cardiac M2 alpha-selective antimuscarinic drugs now available. These results indicate that (+)-biperiden could represent a further valuable tool for the characterization of muscarinic receptor subtypes.
在离体实验中，运用电刺激兔输精管（M1受体）、豚鼠回肠（平滑肌M2β受体）和大鼠左心房（心脏M2α受体）的功能研究方法，考察了比哌立登（biperiden）的（+）-和（-）-立体异构体对不同毒蕈碱受体亚型的亲和力。（+）-比哌立登对M1受体具有最高亲和力（pA2 = 9.07），对心脏M2α受体亲和力较低（pA2 = 7.25），对回肠M2β受体的亲和力处于中等水平（pA2 = 8.27）。（+）-比哌立登区分回肠M2β受体和心脏M2α受体的能力（区分因子 = 10）与4-二苯基乙酰氧基-N-甲基哌啶甲基碘化物（4-DAMP，区分因子 = 9）相似。相比之下，（-）-比哌立登对所研究的所有毒蕈碱受体亚型均显示出低亲和力，但几乎无明显差异（pA2 = 5.59 ± 6.38）。（+）-比哌立登对M1受体和心脏M2α受体有很强的区分能力（区分因子为66），因此其选择性甚至高于哌仑西平（区分因子为28），这使其成为目前最具M1/心脏M2α选择性的抗毒蕈碱药物之一。这些结果表明，（+）-比哌立登可能是进一步表征毒蕈碱受体亚型的有价值工具。
