Study of local anesthetics. Part 79: Physico-chemical properties of piperidinoethyl esters of alkoxymethylcarbanilic acids.

Partition coefficients, pH's of turbidity, surface tensions of aqueous solutions, UV spectra and RF values of the adsorption TLC of the salts of 9 piperidinoethylesters of alkoxymethylcarbanilic acids were measured. The surface and infiltration local anesthetic activities of the compounds were correlated with the determined physico-chemical parameters.

Antiarrhythmic activity of heptacaine and some of its derivatives.

In the evaluation of experimental antiarrhythmic effect in guinea pigs, by a method of antagonizing ouabain arrhythmogenity, there was found a maximum effect of N-[2-(2-heptyloxy-phenylcarbamoyloxy)-ethyl]-piperidinium-chloride (heptacaine). The shortening or prolongation of the alkoxy substitution in the ortho-position, or the shift of hexyloxy substitution to the meta- or para-position, respectively, causes a decrease in activity. Negative chronotropic effect of heptacaine is increased and prolonged during the 5th min after acute i.v. application. The effect of lidocaine was short-lasting and decreased. In antagonizing experimental adrenaline (epinephrine) arrhythmogenity, heptacaine showed an important antiarrhythmic effect, too. In the relative hypotensive activity evaluation, there was an important effect in the 1st min after i.v. application and this decreased to the same values as those of lidocaine in the 5th min. Hypotensive effect evaluation of lidocaine and heptacaine after higher doses than therapeutic ones showed that the hypotensive effect of heptacaine takes place at the same rate as that of lidocaine and by the 10th min reaches control values. Values of experimental partition coefficient showed an increase in relation to prolongation of ortho-alkoxy substitution in the sequence: propoxy less than pentyloxy less than heptyloxy less than nonyloxy. Submaximal value by the heptacaine may reflect an optimal hydrophylic-lipophylic balance of its molecule. But in the evaluation on antiouabain effect and partition coefficient, there is no simple direct correlation in structure-activity relationship.

Study of local anesthetics. Part 46: Correlations between anesthetic activity and physico-chemical parameters of some alkoxy substituted esters of phenylcarbamic acids.

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.