Preclinical toxicologic evaluation of DENSPM (N1,N11-diethylnorspermine) in rats and dogs.
A toxicology study of DENSPM was carried out in rats by multiple (once daily for 5 days) intravenous injection. Doses of 12.5, 25 and 50 mg DENSPM/kg were well tolerated. Infusion of 100 mg DENSPM resulted in distressing physical signs, including labored breathing, convulsive movements and acute death. There were no end-organ toxicities induced by this regimen as evaluated by serum chemistry and hematology examinations, and histopathologic exam of all major body organs. Transient hypotension was induced in rats and dogs by rapid infusion of DENSPM; the magnitude of this hypotension was decreased by slow infusion of DENSPM into dogs. Hypotension appears to be the dose-limiting toxicity of this agent when infused rapidly.
Kanter
P M
PM
James T Grace Jr Cancer Drug Center, Roswell Park Cancer Institute, New York State Department of Health, Buffalo, NY 14263.
Bullard
G A
GA
King
J M
JM
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D007022:Hypotension / Q000139:chemically induced; D008297:Male; D009336:Necrosis; D009928:Organ Specificity; D051381:Rats; D013096:Spermine / Q000031:analogs & derivatives* / Q000633:toxicity
D000970:Antineoplastic Agents; C059685:N(1),N(11)-diethylnorspermine; D013096:Spermine