Can diastereoisomerism of alkoxyphenylcarbamates influence their local anesthetic activity?

The surface local anesthetic activity (LAA) in the homologous series of racemic (+/-)-cis- and (+/-)-trans-N,N-dimethyl-2- (2-alkoxyphenylcarbamoyloxy)cyclopentylmethylamonium chlorides was evaluated. The potency was expressed in rabbits as efficiency indices (EI) in comparison to the standard drug cocaine. All tested racemic mixtures of the phenylcarbamates were local anesthetically active and their potency increased with the size of alkoxysubstitution from the propyloxy- to the hexyloxyderivative and then decreased abruptly (cut-off effect). When different mixtures of both diastereoisomers were applied the synergistic effect--i.e. increase of the LAA of one diastereomer when adding the other--was observed. It seems that an optimal racemic ratio of the compounds could increase their local anesthetic efficiency.