Affinity and selectivity of biperiden enantiomers for muscarinic receptor subtypes

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.