Dropropizine

Abstract: The complex extract and the polysaccharide isolated from the roots of marsh mallow were tested for antitussive activity in unanaesthetized cats of both sexes. Cough was elicited by mechanical stimulation of laryngopharyngeal and tracheobronchial mucous area of the respiratory system with a Nylon fibre (diameter 0.35 mm). Cough was evaluated on the basis of the changes in lateral tracheal pressure. The polysaccharide and the complex extract were administered p.o. in a dose of 50 and 100 mg/kg b.w., respectively. The efficiency of the mentioned compounds was compared with the cough-suppressing effect of drugs belonging to the non-narcotic antitussics. The results of the experiments showed that administration of the polysaccharide led to a statistically significant decrease of the number of cough efforts both from laryngopharyngeal and tracheobronchial areas of the the respiratory system. The polysaccharide in a dose of 50 mg/kg b.w. was as effective in inhibition of the cough reflex as Sirupus Althaeae in a dose of 1000 mg/kg b.w. and more effective than prenoxdiazine in a dose of 30 mg/kg b.w. However, the cough-suppressing effect of the polysaccharide was lower than that of dropropizine. The extract was less effective than the polysaccharide.

Abstract: We studied inhibition of DNA synthesis, alkaline elution of DNA, cytotoxicity and occurrence of induced 6-thioguanine resistant mutants in mammalian cells, treated with mazindol, lithium carbonicum, and dropropizine, respectively, in the presence and in the absence of microsomal fraction S9. Among the above-mentioned clinically used drugs only dropropizine showed neither mutagenic nor clastogenic effects. Lithium carbonicum manifested a weak and mazindol a medium genotoxic response which was in both cases reduced in the presence of microsomal fraction S9.

Abstract: The antitussive activity of levodropropizine (S(-)-3-(4-phenyl-piperazin-1-yl)-propane-1,2-diol, DF 526), was evaluated in anaesthetized guinea-pigs and rabbits and in unanaesthetized guinea-pigs. Levodropropizine was shown to have good antitussive activity. Intravenously, it was 1/10 to 1/20 as active as codeine and comparable to dropropizine, from which it is derived, on mechanically and electrically induced coughing in rabbits and guinea-pigs. After oral administration to the guinea-pig the antitussive activity of levodropropizine was comparable with those of both dropropizine and codeine against coughing induced by irritant aerosols.

Abstract: The general pharmacological profile of levodropropizine (S(-)3-(4-phenyl-piperazin-1-yl)-propane-1,2-diol, DF 526), a new antitussive drug, was compared with that of dropropizine racemate. Levodropropizine had weaker central sedative effects than the racemate and it did not induce physical dependence in rats. When given intravenously or intraperitoneally, levodropropizine did not exert any significant effects on the cardiovascular and respiratory systems. Receptor binding data excluded interaction with beta-adrenergic, muscarinic and opiate receptors. On the contrary, levodropropizine has affinity for H1-histaminic and alpha-adrenergic receptors. The affinity was also confirmed with isolated organ preparations. On the basis of this study, levodropropizine appears to have a better tolerability index than the racemate.