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The spatial arrangement of single stereoisomers may influence pharmacodynamic, pharmacokinetic and toxicological properties of a drug. Trapencaine (I. N. N.), (+/-)-trans-2-(pyrrolidin-1-yl)cyclohexylester of 3-(n)-pentyloxycarbanilic acid, was developed as an antiulcer drug with gastroprotective, local anaesthetic and spasmolytic effects. Limited information is available about the potential pharmacodynamic differences of the enantiomers of trapencaine. Therefore, the enantiomers of (+/-)-trans- or cis-2-(pyrrolidin-1-yl)cyclohexylester of 3-(n)-pentyloxy carbanilic acid were synthesised and tested on models of acute gastric damage induced by indomethacin and/or ethanol. A difference was found between their antiulcer effect, with the (+)-trans-enantiomer being the most effective and the (-)-cis-enantiomer the least effective in the models used.

The effect of cis- and trans-isomers of 2-(1-pyrrolidinyl) and of 2-(1-pyrrolidinylmethyl)cyclohexyl alkoxycarbanilates was tested in acute gastric injury induced by phenylbutazone and/or 96% ethanol administration in rats. In both models a more pronounced antiulcer and gastroprotective activity was observed after pretreatment with the trans-isomer of 2-(1-pyrrolidinyl)cyclohexyl ester of 3(n)-pentyloxycarbanilic acid. Its cis-isomer, by comparison, was less effective against ethanol-induced gastric injury and failed to prevent the gastric damage induced by phenylbutazone. After introducing a methylene group into the hydrophilic part of the molecule, there was a loss of stereospecific difference, with both stereoisomers exerting a similar gastroprotective activity.

The optically active isomers of carbisocaine [1-methyl-2-diethylaminoethyl ester of 2-(n)-heptyloxycarbonilic acid] were prepared. The blocking activity of equimolar concentrations of the carbisocaine and its corresponding enantiomers was tested on isolated rat sciatic nerves. There were no significant differences between the anesthetic action of racemic form and enantiomers, however, lower activity for the (--)-enantiomer was observed. The results may indicate negligible stereoselectivity of action of highly lipophilic local anesthetic carbisocaine in the excitable membrane.

A series of the new aminoalkyl esters of chlor-, methyl- and alkoxy carbanilates was synthesized. All the compounds prepared were found to exhibit antiarrhythmic activities comparable with those of mexiletine.

The genotoxic effect of stobadine (1) was studied in vitro using the micronucleus test. Hamster and human fibroblastoid cells were used. In hamster cells, the highest concentration of 1 (1.10(-3) mol/l) caused a significant elevatin in the number of micronuclei, while in human cells no positive response was found for either of the concentrations used. Stobadine had no genotoxic effect on human fibroblastoid cells.

The partition in water-octanol and water-carbon tetrachloride systems and electronic spectra of three series of esters of phenylcarbamic acid and its m- and p-alkoxy derivatives were measured. The surface local anesthetic activity of these compounds as well as the infiltration anesthetic activity of some of them were correlated with combinations of partition coefficients, spectral parameters and sigma-coefficients.

Pentacaine is a local anaesthetic which exhibited positive effects on healing of model ulcers in the rat stomach. The in situ disappearance of pentacaine from the ulcerous and intact rat stomach was studied. Gastric ulcers were produced by oral administration of phenylbutazone (200 mg . kg-1) 3.5 h before absorption experiment. Pentacaine exhibited a biexponential decrease from the lumen of the stomach, the rate of which was essentially the same in both groups. The total amount of pentacaine absorbed was small because of extremely low absorption rate.