Me> h and bulky group R2=Me, decrease N-effect Triethyl substitution displays M-effect retains anticholinergic effect carbamoyl substitution is stable 2 R Et or ph substitution cation Is important lower activity R As( CH3)3, S(CH3)2 Se(Ch3)2 subtitution decrease the acitivity R3=Me, inhibit AChE N-effect> M-effect