COMPARATIVE TOXICOLOGY OF 2 ENANTIOMERS OF THE PERIPHERALLY ACTING NONNARCOTIC ANTITUSSIVE DRUG MOGUISTEINE

Moguisteine y)-methyl-3-ethoxycarbonylacetyl-1,3-thiazolidine, CAS 119 637-67-1), a new peripheral non-narcotic antitussive drug, is a racema te composed of an equimolar mixture of R(+) and S(-) enantiomers (BBR 2221 and BBR 2222, respectively). Since in some cases the use of only one enantiomer instead of a racemate may Increase the efficacy and/or the tolerability of a compound, moguisteine enantiomers were submitted to toxicological evaluation. Given in a single oral (gavage) or intra peritoneal administration to mice and rats, both moguisteine enantiome rs show very low general toxicity. Administered by gavage to rats and dogs for four consecutive weeks, BBR 2221 and BBR 2222 are tolerated a t up to the dose of 240 mg/kg/day in both sexes with no appreciable to xic changes. Finally, the mutagenicity tests show that both enantiomer s are devoid of any mutagenic potential both in vitro and in vivo. Con sidering the overall results of the toxicological studies and comparin g them with the data obtained from the previously performed studies wi th the racemate moguisteine, it can be affirmed that no differences ca n be identified between the two enantiomers and the racemate moguistei ne. These findings justify the development of moguisteine as a racemat e since neither enantiomer should offer any advantage over the racemat e.