title: Toxicological evaluation of azumolene after repeated intraperitoneal administration in rats.
abstract: We investigated the toxicity of azumolene (Az), a more water-soluble compound than dantrolene, after 14 days of intraperitoneal (i.p.) administration in rats at doses of 1, 2.5 or 10 mg/kg/day. No animals died or presented signs of toxicity. No significant differences in water and food consumption or weight gain were noted among the groups. Blood analysis revealed no significant alteration by Az treatment in the number of blood cells. However, Az treatment induced a perivascular inflammatory reaction in the liver and non-diffuse necrosis of skeletal muscle, both of which occurred only at the highest dose of Az and were completely reversed 14 days after cessation of treatment. Congestion and inflammation in the kidneys were only partially reversed. Caffeine-induced contracture of skeletal muscle was not altered during 7 days of i.p. injection of Az (2.5 mg/kg/day). In conclusion, Az is a safe compound for long-term administration, but does cause a mild, reversible reaction in skeletal muscle and kidney.
authors.affiliation: Programa de Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Av Carlos Chagas 373, Sala 14, Bloco J, Centro de Ciências da Saúde, Cidade Universitária, Rio de Janeiro, Brazil.
authors.forename: Paula Lima
authors.initials: PL
authors.lastname: do Carmo
authors.forename: Gisele
authors.initials: G
authors.lastname: Zapata-Sudo
authors.forename: Margarete Manhães
authors.initials: MM
authors.lastname: Trachez
authors.forename: Maria
authors.initials: M
authors.lastname: das Graças Fernandes Sales
authors.forename: Roberto Takashi
authors.initials: RT
authors.lastname: Sudo
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000737:chemistry / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology; D009465:Neuromuscular Agents / Q000737:chemistry / Q000633:toxicity*; D010080:Oxazoles / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D036401:Toxicity Tests, Chronic
chemical_list: D007093:Imidazoles; D009465:Neuromuscular Agents; D010080:Oxazoles; D002110:Caffeine; C061387:azumolene