[Effects of a (fluorophenyl) piperazine derivative (substance IIIv) on cardiovascular function]. / Ucinky (fluórfenyl)piperazínového derivátu (látka IIIv) na kardiovaskulárne funkcie.

The present paper links up with the study of principal pharmacological effects of newly synthesized aryloxyaminopropanols substituted with 1,4-piperazine derivatives in the hydrophilic moiety of the molecule. The substance with the working name IIIv showing the highest beta-adrenolytical and vasodilating effect underwent further pharmacological evaluations with the aim of contributing to the elucidation of the mechanism of its action. After 7-day administration of the substance in two doses (5 and 50 mg.kg-1), the changes in the reactibility of arterial preparations were investigated on three models of the contraction of the isolated rat aorta (KCl, noradrenaline, and PGF2 alpha) from both qualitative and quantitative views. The results were also supplemented with organometric studies of the effect of the substance in rats.

Relationships between the lipophilicity of some 1,4-piperazine derivatives of aryloxyaminopropanols and their beta-andrenolytic activity.

Nineteen 1,4-piperazine derivatives of aryloxyaminopropanol were evaluated with respect to beta-adrenolytic activity. The retention factors obtained from HPLC, RM values obtained from partition TLC and the lipophilic Hansch's (4) constants pi were determined and the compounds were studied with respect to their lipophilicity based on chromatographic properties. The study of the influence of different substituents introduced at the para position on the phenyl ring on the retention factor indicated the log k vs. the number of carbon atoms in R1 substituent to be a linear relationship. Attempts have been made to relate the beta-adrenolytic activity to the lipohydrophilic parameters by deriving a quantitative relationship between them. Significant parabolic correlation was observed between the beta-adrenolytic activity and the logarithm of the retention factor, log k. An analogous relationship was obtained between the beta-adrenolytic activity of the compounds and the RM values obtained from partition TLC as well as Hansch's lipophilic constants pi.

Comparative studies on beta-adrenolytic potencies of some new phenoxyaminopropanol derivatives and celiprolol.

The influence of different substitutions in 4-position of the phenyl ring of three recently developed l-alkylamino-3-phenoxy-2-propanol derivatives on the beta-adrenolytic potency and tissue specificity has been investigated and compared to the cardioselective beta-adrenoceptor antagonist celiprolol. The pA2 values against the isoprenaline tachycardia in isolated right atria (beta 1) and the relaxation of tracheal muscle (beta 2) both of guinea-pigs were expressed as beta 1/beta 2 selectivity ratio. The efficiencies and cardioselectivity of 4-propoxycarbonylderivative (BL 345 Ac) as well as celiprolol were similar, whereas 4-propoxymetylsubstitution (FoA 34t) decreased the inhibiting potency to the heart tissue nearly three times. The elimination of the 4-substitutent leads to the total loss of cardioselectivity (FoA 04). In addition, the character of the 4-substition has also influenced the nonspecific membrane activity expressed as local anesthetic efficiency in experiments on rabbit eyes and guinea-pig skin.

[Preparation and pharmacologic characteristics of aryloxyaminopropanol derivatives with an assumed cardiovascular effect]. / Príprava a farmakologická charakteristika aryloxyaminopropanolových derivátov s predpokladaným kardiovaskulárnym pôsobením.

In an attempt to prepare drugs favourably influencing pathologically changed functions of the cardiovascular system, such as hypertension and ischemic cardiac disease, several chemical compounds were prepared in which benzhydrylpiperazine, alkyl, or substituted phenylpiperazine (fragments of the structures of calcium antagonists) were bound to the fundamental aryloxyamino-propanol skeleton (the carrier of beta-adrenolytic effect). The selected four compounds underwent basic pharmacological analysis. In experiments on the isolated spontaneously beating guinea-pig atria (beta 1), three compounds competitively inhibited the positively chronotropic effect of isoprenaline (pA2 = 6.40-7.24) and in experiments on the isolated tracheal guinea-pig muscle they antagonised the relaxation effect of isoprenaline beta 2, the pA2 values ranging from 5.90-7.58. It follows from the experiments on the isolated guinea-pig aorta contracted with 50 mM KCl that all compounds under study possess mild relaxation effects, the intensity of which is, however, lower than in the used standards flunarizine and verapamil.