Effect on the peripheral nervous system of the short-term intravenous administration of paclitaxel in the rat.

The effectiveness of paclitaxel (Taxol) in the treatment of different tumors is well-known but, on the other hand, there is little information regarding its neurotoxicity and the mechanism(s) underlying this potentially severe side effect. In this study, using behavioral, neurophysiological, morphological and morphometric methods, we evaluated the effect of intravenous administration of paclitaxel on the rat nervous system. After 2 pilot studies, 40 female Wistar rats were treated with intravenous paclitaxel via a catheter placed in the jugular vein, while 20 animals were used as controls.

Comparative toxicology of two enantiomers of the peripherally acting non-narcotic antitussive drug moguisteine.

Moguisteine (R,S(+/-)-2-(2-methoxyphenoxy)-methyl-3-ethoxycarbonylacetyl-1,3-t hiazolidine, CAS 119637-67-1), a new peripheral non-narcotic antitussive drug, is a racemate 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 intraperitoneal administration to mice and rats, both moguisteine enantiomers show very low general toxicity.

Reproductive toxicology of the new antitussive moguisteine.

Moguisteine (R,S(+/-)-2-(2-methoxyphenoxy)-methyl-3-ethoxycarbonylacetyl- 1,3-thiazolidine, CAS 119637-67-1), a new oral non narcotic peripherally acting antitussive drug, was examined for effects in the rat on general reproductive performance (at 0, 50, 212, 900 mg/kg/d,) for embryotoxicity (at 0, 25, 75, 225, 900 mg/kg/d) and for peri-postnatal toxicity (at 0, 62.5, 250, 1000 mg/kg/d). Embryotoxicity (at 0, 75, 225, 900 mg/kg/d) was also examined in the New Zealand White rabbit.

General toxicology of the new antitussive moguisteine.

Moguisteine (R,S(+/-)-2-(2-methoxyphenoxy)-methyl-3-ethoxycarbonylacetyl- 1,3-thiazolidine, CAS 119637-67-1), a new oral non-narcotic peripherally acting antitussive drug, was submitted to toxicological evaluation. The oral (gavage) and intraperitoneal routes in mice and rats and the oral route in rabbits produce very low acute toxicity. Administered by oral route, moguisteine proved to be well tolerated for 26 consecutive weeks and did not induce any general or local effect at up to the respective doses of 240 and 60 mg/kg/day for rats and dogs.

Acute intravenous toxicity of dimethyl sulfoxide, polyethylene glycol 400, dimethylformamide, absolute ethanol, and benzyl alcohol in inbred mouse strains.

Acute intravenous toxicity of some solvents, i.e. dimethyl sulfoxide (DMSO), polyethylene glycol 400 (PEG 400), dimethylformamide (DMF), absolute ethanol (EtOH) and benzyl alcohol (BeOH), was determined in three inbred (CD2F1, B6D2F1 and C57BL/6N) mouse strains used in many preclinical tests, mainly in oncology and toxicology.