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. In oral (dietary) carcinogenicity studies, moguisteine did not exhibit any carcinogenic effect in mice and rats treated for 87 and 104 weeks, respectively, at up to the dose of 600 mg/kg/day. These results are supported by the absence, both in vitro and in vivo, of mutagenic potential. Considering the overall results of the toxicological studies, it can be affirmed that moguisteine enjoys reliable tolerability, as also shown by a wide safety margin calculated on the basis of the animal and human exposures.
Research Centre, Boehringer Mannheim Italia, Monza, Milan, Italy.
E
E
Cavalletti
R
R
Ceserani
F
F
Sala
P
P
Montaguti
S
S
Tognella
D000818:Animals; D000996:Antitussive Agents / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity; D004285:Dogs; D005260:Female; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008815:Mice, Inbred Strains; D009153:Mutagens / Q000633:toxicity; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000633:toxicity*; D053778:Thiazolidines
D000996:Antitussive Agents; D002273:Carcinogens; D009153:Mutagens; D013844:Thiazoles; D053778:Thiazolidines; C087933:moguisteine