The atropisomeric and conformational properties of the 4-Cl/Me-substituted pirenzepine/telenzepine analogues were examined. Although the 4-substitution is not effective in reducing the rotational barrier of the N5-(C1'=O) bond, the butterfly motion of the tricyclic ring system was frozen. The atropisomers showed little racemization after heating at 80 °C for 5 days. While these analogues showed less affinity to the M1 receptor compared with pirenzepine, a ca. 4.4-fold difference in potency between the atropisomers was observed for 1b.