By using stereospecific reactions we prepared two homological series of diastereomeric + cis- and + trans-N,N-dimethyl-2-(2- alkoxyphenylcarbamoyloxy)cyclohexylmethyl-ammonium chlorides with number of carbons in the alkoxy group varying from one to eight. Structure of the prepared compounds was proved by NMR and IR spectroscopy. The principal physico-chemical characteristics, including partition coefficients, were obtained and relative local anesthetic activity was measured using a surface in vivo model. It was found that (1) for both cis- and trans-isomers there is a parabolic relationship between log activity and molecular lipophilicity (as measured by TLC RM and log P values), (2) all drugs prepared for this study use hydrophobic pathway to block inactivated channels, and (3) there is no strict requirement for precise disposition of the functional groups responsible for receptor binding, probably due to conformational flexibility of the sodium channel protein.